Antimicrobial agent

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ANTIMICROBIAL AGENT
& MECHANISM OF
RESISTANCE
Julia Hartati, dr

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Antimicrobials Agents
Definition Antibiotic is :
A chemical substance produce by microorganism
(natural products) which has the capacity to inhibit
the growth of bacteria, fungi, viruses or protozoa. It
has a high chemotherapeutical index to reduce the
active process in organism in a diluted solution.
Antibiotics = anti microorganisms = anti
microbes
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Classification of antibiotics
1. Based on chemical structures
2. Based on the sources
3. Based on mechanism of action
4. Based on spectrum of action / activity
5. Based on modes of action
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1. Based on chemical structures
1. Groups of sulfonamides  Sulfamethoxazole,
sulfadiazine
2. Groups of Penicillin  Penicillin G
(Benzylpenicillin), Penicillin V,
Ampicillin, amoxicillin, nafcillin
3. Groups of cephalosporins  cefalotin, cefazolin,
cefamandole, cefuroxime, cefotaxime, ceftriaxone.
4. Groups of aminoglycosides  streptomycin,
neomycin, kanamycin, gentamycin, tobramycin
5. Groups of chloramphenicol  chloramphenicol,
tiamphenicol
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1. Based on chemical structures
6. Groups of tetracyclines  chlortetracycline,
oxytetracycline, doxycycline, minocycline HCl
7. Groups of macrolides  erythromycin,
roxithromycin, spiramycin, azithromycin
8. Groups of polyenes  amphotericin B, nystatin
9. Groups of Lincomycins  lincomycin, clindamycin
10. Groups of polymixins  Polymyxin B, Polymyxin E
11. Groups of sulfon  dafsone
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1. Based on chemical structures
12. Other groups  vancomycin,
cycloxerine, bacitracin, metronidazole
13. Groups of quinolones  nalidixic acid,
norfloxacin, ciprofloxacin, offloxacin
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II. Based on the sources
a.Antibiotic from microbes
§A.B. from fungi  Penicillin from P. notatum
§A.B. from bacteria
•A.B. from eubacteria  polymyxin from bacillus polymyxa
•A.B. from micromonosporaceae  gentamyicin from
micromonospora purpurea
b. Antibiotics from algae  Usnat Acid
c. Antibiotics from higher plants  Garlisina from
Allium sativum
d. Antibiotics from animals  Eritrina from
hemoglobin of cow
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III. Based on mechanism of action
A. Inhibition of cell wall synthesis leads to the death
of the bacteria lysis (bactericidal effect) 
penicillin, cycloserine, vancomycin, bacitracin,
cefottaxime, ceftriaxone.
B. Disruption of cell membrane function  polymyxin
(polymyxin B, polymyxin E), polyenes, nystatin
C. Inhibition of protein synthesis:
This antibiotics inhibit one of the reactions in the
process of transcription
1.Inhibition of translation process of microbes
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III. Based on mechanism of action
•Inhibit ribosome on the 30 S subunit 
streptomycin, tetracylines, netilmicin, kanamycin
•Inhibit ribosom on the 50 S subunit 
chloramphenicol, clyndamycin, lincomycin
§Inhibits the transcription process of microbes
 Rifampin, actinomycin
D. Inhibits spesific metabolic reaction
Inhibits the enzymatic reactions 
sulfonamides, INH, PAS, trimethoprim
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IV. Based on spectrum of action
§Broad spectrum: Effective to Gram +, Gram -
bacteria, mycoplasmas, chlamydiae,
rickettsiae, sometimes protozoa 
chloramphenicol, tetracyclines
§Narrow spectrum: Effective to Gram + / Gram -
bacteria only  penicillins, cephalosporins,
erythromycins, polymyxins
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V. Based on modes of action
1938 : N. gonorrhoeae are sensitive to sulfa
1948 : N. gonorrhoeae became resistant, sulfa was
no longer used
N. gonorrhoeae that resistant to penicillin -----
penicillinase producer - strains.
Staphylococcus that resistant to penicillin
beta-lactamase enzymes.
Paul Ehrlich (1902 – 1909) mice infected with Paul Ehrlich (1902 – 1909) mice infected with
trypanosoma and treated with azo dyes, organic arsenyl trypanosoma and treated with azo dyes, organic arsenyl
and triphenyl methone trypanosoma became resistant and triphenyl methone trypanosoma became resistant
after contactedafter contacted with the drugs.with the drugs.
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Mechanisms of resistanceMechanisms of resistance
Bacteria produce enzymes that destroy the active drugs
such as beta-lactamases which will destroy beta-
lactams antibiotics.
Natural resistance :
genetic  chromosomal resistance and
extrachromosomal
resistance
non genetic
Genetic resistance happen because of genetic
changes
Non genetic resistance happen because of antibiotics
come into contact with bacteria which have active
metabolism. FK UNISBA

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Mechanisms of resistanceMechanisms of resistance
Example : M. tbc can persist in the tissues for a
long time. The bacteria persist for years after
infection without replication, due to the good
immune system of the patient.
In this condition M .tuberculosis can not be killed by
antibiotics
Acquired resistance Acquired resistance  Sensitive bacteria will get Sensitive bacteria will get
this resistance properties through plasmid which this resistance properties through plasmid which
contains resistance factors (R factors) from contains resistance factors (R factors) from
resistance bacteria.resistance bacteria.
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Mechanisms of resistance (Weinstein, 1984)Mechanisms of resistance (Weinstein, 1984)
1. 1. Alteration of cell membrane permeability, such
alteration inhibit penetration of antibiotics to
bacterial cell  Staphylococcus against
tetracyclines
2. Alteration in bacterial cell, so that a big ammount of
antibiotic destroy enzymes are produced
b -lactamase against penicillins and cephalosporins
Acetyltransferase against chloramfenicol
Phosphorilase, acetylase and adenylase against
aminoglycosides
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Mechanisms of resistance (Weinstein, 1984)Mechanisms of resistance (Weinstein, 1984)
3. 3. Alteration of receptors usually affects bacterial Alteration of receptors usually affects bacterial
ribosomes. The mutation alters the DNA that ribosomes. The mutation alters the DNA that
produces a ribosomal protein receptor so the a produces a ribosomal protein receptor so the a
antibiotics cannot bind to it antibiotics cannot bind to it  erythromycin erythromycin
receptor in staphylococcusreceptor in staphylococcus
4. Alteration of a metabolic pathway in bacterial cell,
to bypass a reaction inhibited by an antimicrobial
agent  dehidrofolate by trimethoprim,
sulfanomide, INH and PAS
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Some approaches to solve resistance problems
1.Administration of antibiotics prescription only if the
clinical signs and tests indicated that certain
bacteria are the most probable caused of infection
2.Bacteriologic diagnosis must be sought and
susceptibility tests must be determined
3.Avoid the usage of antibiotics which have been
known resistance in one population
4.Reduce the usage of topical antibiotics, use
antiseptics instead.
5.Limit the period of consuming antibiotics
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Some approaches to solve resistance problems
1.Reduce the usage of prophylactic antibiotics
2.Use narrow spectrum antibiotics
3.Always follow directions for use of antibiotics
4.Prescrible antibiotics based on clinical situation
and not on patient’s will or pharmaceutical
advertisements.
Rational drug: drugs given after accurate
diagnosis. It will be effective with minimal side
effects.
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Factors involve in the usage of AB rationally,
effectively and safely.
1.Accurate diagnosis
2.Accurate choices of antibiotics
3.Deliver accurate dose
4.Accurate dosing interval
5.Accurate examinations of patophysiologic conditions
of the patient
Factors involve in choosing antibiotics
Disease factors
Drug factors
Recipient factors
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Factors involve in choosing antibiotics
1.Disease factors
Selective for etiologic bacteria susceptibility test
Types and doses depend on location of infection
Enough penetrating potentials to cross :
•blood-brain barrier in
•abscess walls
§Drugs factors  Ideal antibiotics :
Have a narrow spectrum, affect only to etiologic bacteria
Have a bactericidal effect, unless none is sensitive,
bacteriostatic drugs can be delivered
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Ideal antibiotics :
Effective even in the presence of body fluids
exudate, protein or enzymes.
Ability to reach the infected tissue, enough drug
concentration during the span of a dosing
interval in blood / infected area.
Do not caused resistance
Have a minimal toxic effects for the patient
Safe for pregnancy and pediatric patients
Low costs
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Factors involve in choosing antibiotics
3. Patient factors :
Age
Genetics
Pregnancy
Accompanying diseases
Antibiotic prophylaxis: An antibiotic is used to
anticipate infection from certain bacteria which are
sensitive to the drug.
Goal: To minimize the surgical wound infection, by
treating with antibiotic in lethal concentration for
microorganisms at the beginning of surgery until it
finished (done).
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Sensitivity tests / resistance tests
Qualitative :
§Stokes method
§Ericcson method
§Kirby-Bauer method
§Comparison method
§Quantitative :
1.MIC
2.MIC plate
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Qualitative
The Kirby-Bauer Method: Commonly in
microbiology use the Kirby-Bauer Method . It
use medium of Mueller-Hinton Agar on the
susceptibility test
Mueller-Hinton Agar
Sensitive : clear area (zones of inhibition)
Resistance : No zones of inhibition
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Side effects of antibiotics
§Allergic reaction : Is a respond in sensitive
individual due to the abnormality in his immune
system  Penicillin, Sulfonamides, Streptomycin
Mild symptoms are skin rashes and itching.
Severe symptoms are anaphylactic shock.
§Toxic reaction : Can happen in individual depend
on the doses of drugs in the body  Hearing
disorder because of gentamycin
 Manifestation can occur :
Temporary and permanently
After a prolonged used / acute respond
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Antiviral Agents
1.Inhibit viruses coverage
2.Inhibit DNA and RNA synthesis in the viruses
3.Inhibit protein synthesis in the viruses
4.Inhibit specific enzymes activities in the viruses
5.Inhibit the growth of viruses
6.Promote immunity system of the body
7.Prevent virus infection to the body
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The Drugs that use :
•To inhibit viruses coverage: Amantadine, Rimantidine
•To inhibit DNA and RNA synthesis: Acyclovir,
Ganciclovir, Foscarnet, Ribavirin, Valacyclovir,
vidarabine, cidofovir
•To inhibit return transcription from nucleocid:
Zidovudine, Didanosine, Zalcitabine
•Inhibit protease enzyme Other antiviral drugs:
Idoxuridine, Trifluridine, Fluorouracil, Interferons,
Immunoglobulins
Notes : Antiviral drugs only inhibit the early stage
of replication
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Antifungal Agents
Fungal infection occur less frequently than bacterial or
viral infections.
Three major groups of antifungal agents :
1.Groups of polyenes :
•Amphotericin B
• Nystatin
2.Groups of Azole Imidazoles :
•Ketoconazole
• Miconazole
• Clotrimazole
• Fluconazole
• Itraconazole
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Antifungal Agents
1.Groups of Alilamin:
•Terbinafin
• Naftitin
Other antifungal agents :
Griseofulvin
Flucytosine
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