ANTIMICROBE

AND ITS
RESISTANCE
ERIZKA
RIVANI
 ANTIBACTERIA
01
TOPIC
ANTIFUNGI
02
ANTIVIRUS 03
ANTIMICROBIAL RESISTANCE 04
● SELECTIVE TOXICITY : Clinically
effective antimicrobial agents ANTIBACTERIAL
exhibit selective toxicity toward the
Bactericidal vsbacteriostatic
microbe rather than the host Narrow vs broad spectrum
● Source of AM : antibiotic, synthetic Usually classified by mode of action
chemical, molecular manipulation
of previously discovered
antibiotics
● Antibacterial, antifungal,
antiparasitic,and antiviral
agents
 ANTIBACTERIA
01
TOPIC
INHIBITOR OF CELL
WALL SYNTHESIS

Beta Lactam
Glycopeptide
Monobactam
● Peptidoglycan biosynthesis : (1) synthesis of precursors in the cytoplasm;
(2) transport of lipid-bound precursors across the cytoplasmic
membrane; (3) insertion of glycan units into the cell wall; and (4)
transpeptidation linking and maturation
 BETA LACTAM ANTIBIOTIC

● Beta lactam ring is structurally similar to acyl-D-alanyl-D-

alanine, it binds to enzymes that mediate peptidoglycan
cross-linking inhibition to transpeptidation linking defective
cell wall prone to osmotic instability cell lysis and death
● Enzymes called Penicillin-binding Protein (PBP)
● Also bind to membrane-associated autolytic enzymes
that destroy the cell wall
● Different side chains determine degree of activity,
spectrum, pharmacologic properties, resistance to β-
lactamases
PENICILLIN
● Well distributed to many body compartments - lung, liver, kidney, muscle,
bone, placenta. Penetration into the eye, brain, CSF, and prostate is poor
● Metabolize and excreted by kidney
● Penicillin’s penetration of gram negative outer membrane is often limited
● Resistance to staphylococcal and gram-negative β-lactamases determines
spectrum
● Common reactions to penicillins include allergic skin rashes, diarrhea, and drug
fever
 CEPHALOSPORIN
● Shifting between first- and third-generation cephalosporins gives a wider gram-negative spectrum  by
stability against some b-lactamases found in Gram-negative bacteria
● Fourth-generation cephalosporins have enhanced ability to penetrate outer membrane
● Fifth-generation cephalosporins such as ceftolozane are built to kill highly drug- resistant gram-
negativebacteria
● Cephamycins (extended-spectrum cephalosporin) have marked activity against anaerobes
CARBAPENEM

● Imipenem, doripenem, meropenem, and ertapenem

● Have the broadest spectrum of activity within the β-lactam class combination of
easy penetration bacterial cells and high level of resistance to β-lactamases
(stable against most Ambler class A, C, and D betalactamase
● Imipenem is metabolized and inactivated in the kidneys by a dehydropeptidase I
(DHP-I) enzyme. DHP inhibitor, cilastatin, is combined with imipenem in a 1:1
dosage ratio for clinical use
● Ertapenem is ineffective against Pseudomonas
● All carbapenem available today are administered parenterally
 GLYCOPEPTIDE ANTIBIOTIC
● Vancomycin, teicoplanin
● Binding to the end of peptidoglycan (PG), interfering with transpeptidation
● Glycopeptides bind to the substrate of the transpeptidation enzyme, whereas beta
lactams bind to the enzyme mediating the transpeptidation reaction
● Relatively large size  cannot penetrate the outer membrane of most gram-
negative bacteria to reach their cell wall precursor targets
● Vancomycin can be administered orally or parenterally
● Most frequent side effects of vancomycin are fever, chills, and phlebitis at the site
of infusion. Rapid infusion of vancomycin causes tingling and flushing of the face,
neck, and thorax, known as the “red man syndrome
 MONOBACTAM ANTIBIOTIC

● Aztreonam
● Binds primarily to PBP 3 of Gram-negative aerobes, including P. aeruginosa
● It can demonstrate in vitro synergism when combined with aminoglycosides
● Generally a safe agent, with a toxicity profile similar to those of other b-lactam
drugs
INHIBITOR OF
NUCLEIC ACID
SYNTHESIS

Quinolone
Cotrimoxazole
Rifampin
Metronidazole
 QUINOLONE ANTIBIOTIC
● DNA gyrase and topoisomerase IV
● Fluoroquinolones  oral administration, low protein binding,
good distribution to all body compartments, penetration of
phagocytes, and a prolonged serum half-life that allows once-
or twice-a-day dosing
● Bactericidal, broadspectrum
● Levofloxacin and moxifloxacin have significant activity against
S pneumoniae and Chlamydia, whereas ciprofloxacin is more
useful against P aeruginosa
● Adverse effect: tendinitis, Achilles tendon rupture
 FOLATE INHIBITOR ANTIBIOTIC

● Sulfonamides, trimethoprim, para-aminosalicylic

acid, and
the sulfones
● Frequently, trimethoprim is combined with a sulfonamide
(usually sulfamethoxazole) into a single formulation
(TMP: SMX 1:5 co-trimoxazole)
● Widely distributed in the body, cerebrospinal,
synovial, pleural, and peritoneal fluids, cross the
placenta
● Activity against common bacteria and some protozoa and
fungi
 RIFAMICIN ANTIBIOTIC
● Rifampin exert their bactericidal effects by forming a stable complex with
bacterial- DNA-dependent RNA polymerase, preventing the chain initiation
process of DNA transcription
● Bactericidal against susceptible Gram-positive cocci, well-known
antimycobacterial
effects, selected gram-negative organisms, including Neisseria and Haemophilus
but not members of the Enterobacteriaceae
● Anti biofilmactivity
● Produces a harmless, orange-red coloration of saliva, tears, urine, and sweat
● Rifampin-induced hepatitis, potent inducer of cytochrome P450 enzymes
 METRONIDAZOLE
● Antibacterial action requires reduction of the nitro group under anaerobic conditions
● Therapeutic levels are achieved in all body tissues and fluids, including abscess
cavities and CSF, crosses the placenta and secreted in breast milk
● Drug of choice for the treatment of trichomoniasis, giardiasis, and intestinal and
invasive
amebiasis
INHIBITOR OF
PROTEIN SYNTHESIS

Aminoglycoside
Tetracycline
Glycylcycline
Macrolide
Lincosamide
Streptogramin
Chloramphenicol
Oxazolidinone
 AMINOGLYCOSIDE ANTIBIOTIC
● Gentamycin, tobramycin, amikacin, streptomysin, and kanamycin
● Irreversibly binding to bacterial ribosomes
● Only active to organisms that are able to transport them into the cell by a
mechanism
that involves oxidative phosphorylation
● Toxic to the vestibular and auditory branches of the eighth cranial nerve and kidney
● Often combined with β-lactam antimicrobials
 TETRACYCLINE ANTIBIOTIC
● Tetracycline, doxycycline, andminocycline
● Binding reversibly to the 30S ribosomal subunit
● Glycylglycine antibiotic agents are semisynthetic tetracycline derivatives –
Tygecycline, refractory to the most common tetracycline-resistance mechanisms
● Tetracyclines are absorbed orally, whereas tigecycline is not
● Tetracyclines are chelated by divalent cations, which may reduce their absorption
and activity
● Dental staining and enamel damage to permanent teeth limits use of tetracyclines in
young children
 CHLORAMPHENICOL ANTIBIOTIC
● Available for topical, oral, or parenteral use
● Diffuses well into many tissues and body fluids, including CSF. Crosses the
placental barrier and is present in human milk
● Bone marrow toxicity, gray baby syndrome
 MACROLIDES ANTIBIOTIC
● Erythromycin, azithromycin, andclarithromycin
● Bind reversibly to the 23S rRNA of the 50S ribosomal subunits , thereby blocking
the translocation reaction of polypeptide chain elongation
● Tissue distributions of macrolides are excellent, penetrate poorly into the brain and
CSF, do cross the placenta and are excreted in breast milk
● Bacteriostatic
● Relatively broad-spectrum antibiotics, with activity against Gram-positive and
some Gram-negative bacteria, mycoplasmas, chlamydiae, treponemes, and
rickettsiae
● Erythromycin-resistant strains display cross-resistance to clarithromycin and
azithromycin
 LINCOSAMIDE ANTIBIOTIC
● Lincomycin, clindamycin
● Distributes well into bone, lungs, pleural fluid, and bile, but it penetrates poorly
into CSF, crosses the placenta and enters fetal tissues
● Clindamycin is actively concentrated in neutrophils and macrophages
● Broad spectrum of activity against the aerobic Gram-positive cocci and one of the
most active antibiotics available against anaerobes
 STREPTOGRAMIN ANTIBIOTIC
● Quinupristin and dalfopristin are used in a synergistic combination
● Clinical use thus far has been limited generally to the treatment of
VRE

OXAZOLIDINONE ANTIBIOTIC
● Linezolide
● Activity against gram-positive bacteria resistant to other
agents
● Clinically useful in pneumonia and soft tissue infections
 ANTIFUNGI
02
TOPIC
CYTOPLASMIC MEMBRANE AGENT

● The major limitation of AmpB use is toxicity  renal

failure
● Can be given orally
or parenterally
● Generally well-tolerated,
can cause varying degrees
of liver toxicity
● Additionally, all systemic
azoles,
except isavuconazole, can
placing patients at
increased risk for cardiac
arrhythmias
 NUCLEIC ACID SYNTHESIS AGENT

● Well absorbed after oral administration

● Active against most clinically important yeasts
● Resistance develops during therapy if used alone
● Primary toxic effect of flucytosine is a reversible bone marrow
suppression
 CELL WALL INHIBITOR AGENT

● Act by inhibition of a glucan synthetase (1,3-β-D-glucan synthetase)

● Cryptococcus neoformans whose cell wall glucans have a slightly different
structure
is resistant
 OTHER AGENT

● Microtubule disruption interferes with cell division

● Active against dermatophytes
● Iodide inhibits Sporothrix
 ANTIVIRUS
03
TOPIC
 STRUCTURE
DNA or RNA, a protein
coat (capsid), and, in JUPITER
many, a lipid or
Despite beingred, It’s the biggestplanet in
lipoproteinenvelope
Mars is a cold place, our SolarSystem
not hot

Events in the cell

unique to viral SATURN NEPTUNE
replication are the
most desirable targets Saturn is the ringed Neptuneis the farthest
for antiviral therapy planet and a gas planet from the Sun
giant
 INHIBITOR OF ATTACHMENT
● Antibodies can bind to the extracellular virus and prevent this attachment.

INHIBITOR OF PENETRATION AND

UNCOATING
● Rimantadine, amantadine : extremely selective, with activity against only
influenzaA, where they act as inhibitors of the viral M2 protein
 NEURAMINIDASE INHIBITOR
● Oseltamivir, zanamivir
● Inhibit the neuraminidase of influenzaA and B viruses: cleaves terminal sialic acid
from glycoconjugates and plays a role in the release of virus from infected cells
● Reduces influenza symptoms, shortens the course of illness by 0.5 to 1.5 days, and
reduces the rate of complications
 NUCLEOSIDE ANALOGUE
● Active against virus-specific nucleic acid polymerases or reverse transcriptases and
have much less activity against analogous host enzymes
● Idoxuridine, trifluorothymidine is a halogenated pyrimidine that blocks nucleic
acid synthesis by being incorporated into DNA in place of thymidine and
producing a nonfunctional molecule  topical application for herpes keratitis
● Acyclovir : guanosine analogue, it must be phosphorylated by viral thymidine
kinase to be active (effective against the herpesviruses). Available in topical, oral,
parenteral
● Agents that are similar to or become acyclovir after absorption are available
(valacyclovir, famcyclovir, penciclovir)
● Gancyclovir does not utilize viral thymidine kinase for phosphorylation  50
times more activity against CMV than acyclovir
INHIBITOR OF VIRAL DNA SYNTHESIS AGENT
● Foscarnet inhibits viral DNA polymerases, effective against resistant CMV and HSV
● Interferons are host cell-encoded proteins synthesized in response to double-
stranded RNA (dsRNA) that circulate to protect uninfected cells by inhibiting viral
protein synthesis for chronic active hepatitis B and C infection
● Ribavirin has several modes of action : use for RSV infection
 ANTIMICROBIAL
RESISTANCE
04
TOPIC
ANTIMICROBIAL RESISTANCE
This serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has
the potential to affect anyone, of any age, in any country
MECHANISM OF ANTIMICROBIAL RESISTANCE
Resistance arises through one of three mechanisms:
1. Natural resistance in certain types of bacteria
2. Genetic mutation
3. By one species acquiring resistance from another: through conjugation, transduction, or
transformation
MECHANISM OF
ANTIMICROBIAL
RESISTANCE
• The accumulation of these
resistances in the same
bacterium leads to multidrug
resistance or even total
resistance can lead to
therapeutic impasses
• Some bacterial species
frequently involved in human
pathology and often resistantto
multiple antibiotics have been
grouped under the anagram
“ESKAPE”
MECHANISM OF AMR SPREADING
One mutated bacteria then can spread
by..
1. Selective Pressure
2. Contact spreading

4
4
GOALS

MERCURY
Mercury is the smallest planet in our
Solar System. In fact, it’s only a bit larger
than our Moon

JUPITER
Despite being red, Mars is a cold place,
not hot. It’s full of iron oxide dust, which
gives the planet its reddish cast
HOW CAN WE FIGHT AMR?

Penerapan penggunaan antibiotik secara

bijak (prudent use of antibiotics) melalui
penatagunaan antimikroba (antimicrobial
stewardship program) 4
6
Mercury is the closest planet to the Sun and the
smallest one in the Solar System—it’s only a bit
larger than our Moon. The planet’s name has
nothing to do with the liquid metal since it was
named after the Roman messenger god, Mercury