5/18/25, 8:03 AM
print.html
Action and use of Isoniazid
and Ethambutol in
Mycobacterium infection
control.
-antituberculosis drug inhibit
mycolic acid synthesis
-rifampin (rifamycin
antibiotic)
Action of penicillinase (beta
lactamase) and its outcome
(penicillinoic acid).
-natural penicillins are
susceptible to penicillinase (β
lactamase) encoded by R
plasmid
-cleaves the β lactam ring
-antibiotic is inactivated and
bacteria grows in the presence
of antibiotic
Advantages of semisynthetic
antibiotics.
-more effective against Gram
negative bacterial cells
-long lasting
-easier to administer than
some of the normal
antibiotics
Antibiotics safety and use in
pregnant women.
-prescribing antibiotic often
involves assessing risk and
benefits (in
term of therapeutic index )
-often, 2nd drug use may
have a toxic effect that is not
there when
the 1st drug is taken alone
-also, one drug may neutralize
the intended effect of the
other
eg. few antibiotics dampens
effectiveness of contraceptive
pills
- hypersensitivity towards
penicillin antibiotic
-pregnant women should be
given antibiotics that are
considered safe
as recommended by FDA
- there should be no/minimal
risk to the developing fetus
Antibiotics that disrupts
membrane integrity with
example.
Mediated mainly by the
polypeptide antibiotics
eg. Polymixin B
- binds to the cell
phospholipids; disrupts
membrane structure
- alters membrane
permeability
consequence cellular content
leaks out (cell dies)
- limited to topical
applications
Daptomycin: inserts into
bacterial cytoplasmic
membrane
- useful in treatment of some
Gr (+)ve bacteria resistant to
other drugs; not so effective
against Gr (-)ve bacteria
(outer membrane)
Bacteriostatic vs
bactericidal(bacteriolytic)
agents with examples
-bacteriostatic stops bacterial
multiplication
eg. antibiotics targeting
bacterial protein synthesis
tetracycline
bactericidal (bacteriolytic)
kills bacterial cells
eg. penicillin
file:///home/rahul/Desktop/print.html
1/11
5/18/25, 8:03 AM
CNS and bladder bacterial
infection and their treatment
option.
-challenge to treat because of
blood brain barrier
Define/recall antibiotics,
antimicrobial drugs and drugs
with specific
examples.
-antibiotic is a substance
produced in minute quantity
by some microbes that has the
potency to inhibit growth or
kill other microorganisms.
eg. penicillin G
-drug: an agent that affects
physiology
eg. caffeine
file:///home/rahul/Desktop/print.html
print.html
Concept of broad and
extended penicillins with
examples.
-semi synthetic antibiotics are
broad spectrum because they
target both Gram + and bacteria.
eg. ampicillin, amoxicillin
Concept of vertical and
horizontal evolution of
antibiotic resistance.
-vertical gene transfer (VGT)
occurs when resistance genes
are passed down from parent
to offspring during cell
division
-horizontal gene transfer
(HGT) involves the exchange
of genetic material between
different bacteria, even across
different species via
conjugation, transformation,
or transduction
Drugs susceptibility vs
sensitivity concept.
-a microbe may be
susceptible to drug action but
humans can
develop allergic sensitivity to
the drug
Explain drug antagonism and
synergism providing
examples.
-synergism: two drugs given
simultaneously, antimicrobial
effect is
greater than either given
alone
- given individually works
poorly, but well if combined
eg. streptomycin and
penicillin/vancomycin
-antagonism : two drugs when
given simultaneously, their
action
interfere with each other
eg. tetracycline
(bacteriostatic) and penicillin
(bactericidal)
2/11
5/18/25, 8:03 AM
Explain how beta lactam
group differs from non beta
group of antibiotics.
Provide/recall examples of
both groups.
-beta lactam antibiotics
competitively halt activity of
PBP
eg. lactamase sensitive
- Penicillin G
lactamase resistant
-semisynthetics eg.
ampicillin, methicillin
-cephalosporins
-monobactams
-nonbeta lactam group target
different biological processes.
eg. vancomycin
bacitracin
Identify consequences of
antibiotic resistance.
Consequences
i. prolongs infection
ii. delays recovery time,
increases hospital and health
care costs
iii. needs more expensiveand
less effective, toxic
medications to cure
infection
iv. causes higher mortality
rates
file:///home/rahul/Desktop/print.html
print.html
How is R plasmid
transmitted?
Significance of the R plasmid.
-carry 6-7 genes; each confers
resistance to different
antibiotics
-they can be
transferred/acquired by one of
the many genetic
exchange processes
(transduction or conjugation)
How’s vancomycin is
administered to patients?
Is it effective in treatment of
gut bacterial infection?
Its sensitivity to acidic pH of
stomach and absorption.
Its effectiveness against Gr
(-)ve bacterial infection?
-not effective against Gram
(-) ve bacterial cells unable to
penetrate outer membrane
-poorly absorbed,
administered IV, except when
treating intestinal
bacterial pathogens (primarily
effective)
Identify difference between
semisynthetic antibiotics and
synthetic drugs.
Provide examples.
-semisynthetic: antimicrobial
agent partly synthesized in
lab and partly
synthesized in microbes
eg. doxycycline, methicillin,
ampicillin, amoxycillin
-synthetic drug: antimicrobial
agent synthesized in
laboratory.
eg. Isoniazid, sulfa drugs
Identify members of the non
beta group of antibiotics, their
mode of action and
properties: Vancomycin and
Bacitracin.
-vancomycin binds to
terminal amino acid of the
tetrapeptide chain
-prevents cross linking;
weakens cell wall
-bacitracin inhibits
peptidoglycan precursors
(NAG and NAM) transport
across membrane
-toxic, restricted for topical
applications (first aid
ointment)
3/11
5/18/25, 8:03 AM
Identify some clinical uses of
sulfa drug.
Clinical uses of sulfa drug:
-use for UTI treatment
because it can withstand
chemical composition of
urine
-used as a cream of silver
(sulfadiazine) on burn victims
skin because Ag denatures
protein
-used in AIDS cocktail of
drugs to prevent opportunist
microbial infections
file:///home/rahul/Desktop/print.html
print.html
Identify the specific enzyme
sulfa drug targets.
Do we have that specific
enzyme?
How humans get their folic
acid?
-DPS
-humans do not use PABA to
make folic acid using DPS
-green leafy vegetables and
meat
List and recall 5 different
modes of antibiotic action.
• Plasma membrane injury:
disruption of its function /
integrity
• Inhibition of cell wall
synthesis: targets
peptidoglycan
eg. Penicillin
• Blocking protein synthesis:
due to structural
differences of ribosomes (70S
vs 80S human ribosome)
• Nucleic acid synthesis
inhibition: targets enzymes
DNA/RNA synthesis
• Inhibition of general
metabolic pathways: blocking
synthesis of essential
metabolites (action as an
antimetabolite)
eg. sulfa drug inhibits folic
acid synthesis
4/11
5/18/25, 8:03 AM
Mechanism of antibiotic
resistance.
Identify the 5 ways.
–Inactivation or destruction of
the drug
• β lactamase converts
penicillin to penicillionic acid
(no antimicrobial property)
–Prevent antibiotic from
reaching it’s target site /
decreased uptake
• Alteration of the membrane
transport proteins or porins
–Alteration of drug target site
/ enzyme
• Ribosomes
• Enzymes, ex DNA gyrase,
RNA polymerase
-Rapid efflux of the drug
• Pumps the drug out of the
cell before it can become
effective
-Development of alternate
biochemical pathways
• common amongst the
sulfonamide resistant strains
• abandon sensitive steps
-Survival and multiplication
of a mutant variety
file:///home/rahul/Desktop/print.html
print.html
Mode of action of the beta
lactam group of antibiotics?
-interference with linking
enzyme (PBP), NAM
subunits remain unattached,
integrity of peptidoglycan is
compromised, resulting in
cell death due to osmotic
pressure
Monobactams: its use (for
penicillin allergy patients).
Do they belong to beta lactam
or non lactam group?
-have only 1 ring in its
structure
-are given to patients allergic
to penicillin
-beta lactam antibiotic
5/11
5/18/25, 8:03 AM
Penicillin allergy mechanism.
-penicillin is degraded by
liver. penicilloyl binds to
serum proteins acts as
HAPTENS triggering IgE
resulting in anaphylactic
shock, which is concerning
for penicillin allergic patients.
Rifamycin and
ciprofloxacillin action.
Target enzymes for these
antibiotics (gyrase and RNA
polymerase).
-Rifamycins: inhibit RNA
synthesis binds and blocks
prokaryotic RNA polymerase
activity
eg. Rifampin
-quinolones and
fluoroquinolones: specifically
targets prokaryotes
-inhibits bacterial DNA
gyrase (relieves strain caused
by local
uncoiling )
-effective against UTI
pathogens and anthrax ()
-limited use in children and
pregnant women (affects
cartilage development)
eg. Ciprofloxacin
file:///home/rahul/Desktop/print.html
print.html
R plasmid and its role in
antibiotic resistance.
-code for enzymes that
chemically modify the
antibiotics
Recall
advantages/disadvantage of
broad spectrum antibiotic
over narrow spectrum
antibiotic.
Isoniazid belongs to which
group and why?
-broad spectrum targets Gram
+ and - bacteria, however,
disturbs normal microflora
and opens door to opportunist
microbes (causes super
infection)
-narrow spectrum
antimicrobial action is limited
to few sps
eg. Isoniazid because it only
targets Mycobacterium sps
Role of folic acid in bacterial
cell metabolism.
-produces A G T C
nucleotides for nucleic acid
synthesis
Routes of antibiotic
administration with
advantages and
disadvantages.
-can be via external or
internal route
-topical/local application:
applied on skin directly
eg. Polymyxin B
-Internal: administered via
orally, IV, or IM
-orally: simple, no needle or
provider’s help
disadvantage: don’t follow
time table
-intramuscularly: slow
diffusion via blood vessels
disadvantage: high
concentration can’t be
achieved
-intravascular: via needle or
catheter
-can attain high concentration
for limited time (rapid
elimination by liver and
kidney)
6/11
5/18/25, 8:03 AM
Stability and bioavailability
of antibiotics.
Stability: should be stable in
body fluids and exhibit
therapeutic effect;
-not degraded by stomach
acids
-antibiotics prone to
inactivation in gastric
environment should be given
via IV/ IM route
Agent should be bioavailable
-be able to penetrate host
tissue and reach microbial
colony
-must be effective at low, non
toxic concentration to host
file:///home/rahul/Desktop/print.html
print.html
Sulfa drug and its action to
kill bacterial cells.
-sulfanilamide inhibits
Dihydropteroate synthase
(DPS) by competitively
binding its active site
Tissue distribution, concept of
half life, drug detoxification
and excretion.
-all antibiotics are detoxified
by liver and excreted by
kidneys
-half life is the time it takes to
eliminate one half of the
original antibiotic dose in
serum
7/11
5/18/25, 8:03 AM
Types of antibiotic resistance:
3 types.
–chromosomal resistance
–extrachromosomal resistance
–nongenetic resistance
file:///home/rahul/Desktop/print.html
print.html
What are side effects of
antibiotics?
Toxicity of chloramphenicol,
tetracycline , ciprofloxacillin,
penicillin allergy and others.
-trigger allergic reactions
e.g. penicillin allergy
fever, rash and/or
anaphylactic shock
-exhibit toxic effects, though
selective toxicity
e.g. ciprofloxacilin: limited
use in pregnant women and
children (affects cartiliage
development)
chloramphenicol: causes
aplastic anemia (low TI)
polymyxin B: toxic to
kidneys; so not useful for
systemic use (topical use
only)
tetracycline: forms Calcium
complex, limits availability
streptomycin: impairs
balancing sense and may
cause deafness
-disruption of the normal
flora
yeast overgrowth causing
vaginitis or thrush
pseudomembranous colitis to
Clostridium difficile
pseudomembranous patches
(dead epithelial cells,
inflammatory cells, and
clotted blood) causing fever,
abdominal pain, and
diarrhea.
black hairy tongue following
metronidazole treatment
teeth discoloration due to
prolong tetracycline use
What’s Bactrim (Septra)?
Do they belong to sulfa
drugs?
Do they act as
antimetabolites?
-septra/bactrim: contains
sulfomethoxazole and
trimethoprim
sulfa drugs that act as
antimetabolites
synergistic effect
8/11
5/18/25, 8:03 AM
print.html
What’s additive action of an
antibiotic.
-additive: drug combination
that are neither antagonistic
nor synergistic in action
Why Isoniazid and
Ethambutol are needed to be
given to patients for long
period of time?
Due to the slow growth rate
of Mycobacterium sps (longer
generation time).
Why bacteria can’t use our
folic acid?
i. folic acid fails to diffuse
across membrane; because it
is a large molecule
ii. bacteria have evolved with
NO transport system to
uptake folic acid
from environment
iii. additionally, the
architecture of the cell wall
prevents uptake of folic acid
Why polymyxin B is limited
to topical application?
-causes kidney failure
Why rifamycin is effective for
tuberculosis treatment?
Why these antibiotics have
restricted use?
-effective
against Mycobacterium
sps due to its
extended generation time (2448 hours compared to E.coli
20 mins)
-used with caution, since
interferes with mammalian
counterpart
Action of chloramphenicol.
-chloramphenicol binds to
50S subunit of ribosome and
prevents peptide bond
formation (inhibits peptidyl
transferase)
-used as a last alternative due
to its lethal side effect
(aplastic anemia)
file:///home/rahul/Desktop/print.html
9/11
5/18/25, 8:03 AM
Antibiotics that targets
codon:anticodon interaction.
-tetracyclines cause
interference codon: anticodon
interaction;
prevents continuation of
protein synthesis
- selective toxicity: greater
concentration in bacterial
cells than in humans, does not
penetrate very well
mammalian cells (cholesterol
in membrance)
-resistance is due to decrease
uptake / increased “throw
off”,
leads to less “effective”
concentration inside cells
-tetracyclines and Ca ++
metabolism : forms Ca
complex limits availability
Ex: doxycycline,
oxytetracycline,
chlorotetracycline
file:///home/rahul/Desktop/print.html
print.html
Define antimetabolite?
Provide examples and their
mode of action.
-antimetabolite: substance
that prevents a cell from
carrying its
normal metabolic reaction
-antimetabolites are
structurally similar to normal
used molecules
-functions in 2 ways:
– competitive inhibition of
enzymes
eg. sulfanilamide and other
sulfa drugs
– by being erroneously
incorporated into molecules
like nucleic
acids
Recall antibiotics that target
small/large ribosomal unit.
-aminoglycosides :
-bind irreversibly to small
ribosomal subunit (30S)
distorts shape, stalls
initiation; misreads mRNA
codon
eg. streptomycin, neomycin
-macrolides :
-bind reversibly to large
subunit of ribosome (50S)
inhibits
translocation of ribosomes
eg.erythromycin
10/11
5/18/25, 8:03 AM
Selective toxicity
-harm the microbe without
significant damage to the host
-exploits some key aspects of
microbe physiology that is
different from eukaryotes
(peptidoglycan, ribosomes,
etc.)
-shouldn’t be influenced by
food or disease status
file:///home/rahul/Desktop/print.html
print.html
Sulfamethoxazole and
trimethoprim action in
blocking folic acid synthesis.
-Septra/Bactrim has
synergistic effect
If sulfa drug fails to bind DPS
and synthesis cascade
continues, TMP blocks
enzyme further along folic
acid synthesis
-sulfa drugs deplete the cell of
metabolites
Therapeutic Index drugs with
examples. Low TI and High
TI
-lowest dose toxic to the
patient divided by therapeutic
dose
-therapeutic dose: minimum
dose per kg body weight that
stops
pathogen growth
High therapeutic index
-less toxic to patients
-targets uniques points in
bacteria
eg. penicillin, ampicillin,
sulfa drug
Low therapeutic index
-dose must be carefully
monitored as not to reach
toxic level
eg. chloramphenicol
11/11