ANTIBIOTIC DRUGS

Created by group 9 :
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Sekolah Tinggi Ilmu Farmasi

Yayasan Pharmasi Semarang

Abstract
Terminology antibiotics defined as an organic compound of the metabolism
of microorganisms has the ability to inhibit the growth of other microorganisms
and even shut down due to the activity of a small amount of the antibiotic
compound. Antibiotics have a very wide usefulness in the field of pharmaceutical
and agricultural and differentiated antibiotic that is anti-bacterial or antimicrobial, anti-fungal and anti-tumor. Penicillin, tetracycline, erythromycin and
streptomycin are examples of antibiotics that are anti-bacterial.
Keyword :
A. Introduction
Antibiotics derived from the Latin consisting of anti = opponent, bios = life.
Antibiotics are substances produced by microbes, especially fungi and soil
bacteria, which can inhibit microbial growth or eradicate other types, while their
toxicity to humans is relatively small. Antibiotics were first discovered by the
British scholar dr.Alexander Fleming (penicillin) in 1928. But this discovery
newly developed and used in the therapy in 1941 by dr.Florey. Then many of the
substances with antibiotic effects isolated by investigators - other investigators
around the world, but its toxicity is only a few can be used as medicine.
Antibiotics can also be made synthetically or semi-synthetic. There are two kinds
of antibiotics are narrow-spectrum that serves to kill strains of bacteria that are
specifically and broad spectrum as the killer of all bacteria present in the human
body.
B. Mechanisms of Antibiotic
Mechanism of action of antibiotics, among others:
a) Inhibit cell wall synthesis, resulting in the formation of the cell wall is not
perfect and can not withstand the osmotic pressure of the plasma, the cell
eventually will break, such as penicillins and cephalosporins.
b) Inhibit the synthesis of the cell membrane, lipoprotein molecules from the
cell membrane disrupted formation, to be more permeable as a result of

essential substances from the cell contents can come out as a group of
polypeptides.
c) Inhibiting cell protein synthesis, cell consequently not perfectly formed
such

as

clindamycin,

lincomycin,

chloramphenicol,

macrolides,

tetracycline, gentamicin.
d) Disrupt the formation of nucleic acids (DNA and RNA) as a result the
cells can not thrive as metronidazole, kinolon, novobiocin, rifampicin.
e) Inhibit the synthesis of folate such as sulfonamides and trimethoprim.
C. Side Effects of Antibiotics
The side effects of antibiotics, namely:
a) Sensitisation / hypersensitivity, such as itching, skin redness, bumps or a
more

severe

shock

can

occur.

For

example,

penicillin

and

chloramphenicol.
b) Resistance, occurs when the drug is used at a dose that is too low or less
long treatment time. To prevent resistance to chemotherapy is
recommended to use the right dose or by using a combination of drugs.
c) Superinfection, ie secondary infections arising during treatment where the
nature and cause different infections with infectious causes first. In
addition to antibiotics that suppress the immune system of corticosteroids
and other imunosupressiva can cause superinfection.
D. Classification of Restistance
The resistance of microorganisms can be divided into innate resistance
(primary), resistance is acquired (secondary), and resistance episomal.
Primary resistance (default) is the resistance that is the nature of
microorganisms. This example can be caused by antibiotic-degrading
enzymes in microorganisms that naturally microorganisms can break down
antibiotics. Examples adalahStaphylococcus and other bacteria that have
penicillinase enzyme that can break down penicillins and cephalosporins.
This innate resistance mechanisms may also be the presence of a special
structure in bacteria that protect them from exposure to antimicrobials,

such as tuberculosis and leprosy bacterium has a capsule to the cell wall,
making it resistant to antimicrobial drugs.
The mechanism of secondary resistance (acquired) obtained as a result of
contact with the antimicrobial agent in quite a long time with a high
frequency of, allowing the occurrence of mutations in microorganisms.
The formation of mutants that are resistant to antimicrobial drugs can
quickly (resistance one level) and can also occur within a period of time
(multi-level resistance). one example resistance level is at INH,
streptomycin, and tifampisin; and examples of multilevel resistance is
resistance to penicillin, erythromycin, and tetrasiklin.terbentuknya mutant
microorganisms resistant to these antimicrobials may lead to dependence
(dependency) mutant microorganisms tehadap antimicrobial agent.
The mechanism of acquired resistance may also take place due to the
mechanism of adaptation or adjustment of the metabolic activity of
microorganisms to resist the effects of drugs, for example, by changes in
the pattern of the enzyme. Thus, microorganisms can form an enzyme
which describes antibiotic. For example the formation of penicillinase
enzymes to decompose penicillin, the enzyme asetilase to streptomycin,
kanamycin and neomycin.
Acquired another resistance mechanism is to strengthen diding
microorganism cells so that it becomes impermeable to the drug, and
change sides diding cell adhesions. Unisex mimroorganisme releasing
diding cell so that it becomes desensitized to penicillin, for example, the
L-shaped bacteria
Episomal resistance caused by genetic factors beyond the chromosomal
(episomal = plasmid in the plasmids which can be transmitted to other
bacterial species that have connection through cell contacts in conjugation
or transduction. For example Salmonella, Escherichia, Yersinia, Klebsiela,
Serratia, Proteus.
E. Various Kinds of Antibiotic Resistance Against Antibiotics
Resistance to penicillin and cephalosporins
Penicillins and cephalosporins inhibit penicillin-binding

proteins

(penicillin-binding protein, PBP) which is an enzyme in the cell plasma

membrane of bacteria that are normally involved in the addition of amino

acids crosslinked with bacterial cell wall peptidoglycan. Resistensin
bacteria to penicillin may arise as a result of mutation that results in the
production of penicillin binding different production or due to bacteria
require protein genes pengiakt new penicillin. Resistance to penicillin may
also arise as a result of the bacteria have a system transfor outer membrane
(outer membrane) is limited, which prevents penicillin reaching the
cytoplasmic membrane (the location of penicillin-binding protein). This
can occur due to mutations that alter the etrlibat Porin in transport passing
through the outer membrane. Another thing that allows the occurrence of
bacterial resistance to penicillin and cephalosporins is when bacteria have
the ability to produce -lactamase, which hydrolyzes the -lactam ring of
the penicillin molecule and results in inactivation of antimicrobials.
Pathogenic microorganisms resistance to penicillin and cephalosporin
most often caused by the bacteria have a gene encoding -lactamase.
There are three major classes -lactamase, ie penicillinase, oksasilinase,
and karbenisilinase. Penicillinase has a wide range of activity against
penicillin and selafosporin, while oksasilinase and karbenisilinase activity
has been more limited.
In enteric bacteria (facultative anaerobic gram-negative bacteria found in
the human intestinal), -lactamase produced in low concentrations, and
bind to the outer membrane. This prevents the enzyme -laktan
antimicrobial to achieve the target site in the cytoplasmic membrane by
way of destroying it when it passed through the antimicrobial outer
membrane and periplasmic layer (periplasmic space). The gene encoding
the -lactamase present in the bacterial chromosome, in keeping the
bacterial strain is also present in plasmids and transposons. Most
penisilinjuga resistant bacteria have the -lactamase gene in the plasmid
especially a plasmid R and tranposon. -lactamase gene were most
numerous widely is the TEM-1 contained in transposon Tn4.
Methicillin-resistant staphylococci caused by penicillin-binding protein
production naturally PBP 2a or 2 'which has a low affinity to the binding

methicillin. Resistance properties of the bacterial chromosome encoded by

the gene (mecA) that are not found in all strainStaphylococcus aureus,
methicillin-sensitive. This gene appears to be limited to Staphylococci, but
other genes on Streptococci also encodes PBP has a low affinity to
methicillin and antimicrobial -lactam other.
Against Vancomycin Resistance
Vancomycin resistance developing due to the enzyme in bacterial cells
yyang resistant, which would throw an alanine residue from the peptide
peptidoglycan. Vancomycin is bound to the peptide can not change, but the
change peptides that can continue to function in the formation of
crosslinks during peptidoglycan synthesis, thus vancomycin-resistant
bacteria can still create a functional cell wall.
Resistant to tetracyclines
Bacterial resistance to tetracyclines can arise when different generated
cytoplasmic membrane (shape changes) and preventing the binding of
tetracycline to the 30S subunit of the ribosome, so that protein synthesis
can continue. Other tetracycline resistance mechanisms is resistance eflux
pump, based on tetracycline transport out of the cell quickly, thus
preventing the accumulation of the toxic dose tetracycline, sehungga
bacterial protein synthesis is not inhibited. This occurs due to mutations in
the gene that causes the protein eflux tetracycline.
Normally, when tetracycline diffuse across the cytoplasmic membrane of
bacteria, tetracyclines are converted into ionic form. This makes
tetracycline is no longer able to diffuse through the membrane, causing the
accumulation of tetracycline in cells, which eventually can inhibit bacterial
protein synthesis and causing bacterial cell death.
Protein eflux tetracyclines are protein cytoplasmic membrane which
transports the form nondifusible tetracycline come out the cytoplasm. In
bacterial cells that are resistant, tetracycline excluded from the cytoplasm
as soon as its diffusion into the cells, thus preventing the accumulation of
tetracycline to inhibit protein synthesis.
Resistance against aminoglycosides
Aminoglycoside class antibiotic resistance arises because of bacterial cells
produce enzymes that can add phosphate, acetate, or adenyl group on

various places on the aminoglycoside antibiotics. Aminoglycoside

antibiotics that have been modified will not be capable of binding to the
30S subunit of the ribosome so it is no longer able to inhibit protein
synthesis.
Basically, the enzymes that have been used to modify aminoglycosides
will not be able to modify other aminoglycosides. This prevents additional
mutations that will increase Kisara modification of aminoglycosides by
aminoglycoside-modifying enzymes. For example, the footprint bond
modified by a charge-sreptomisin resistant to change an amino acid in the
protein S12 on the 30S subunit of bacterial ribosomes. Semisynthetic
derivative of aminoglycosides further designed to be resistant to the
aminoglycoside-modifying enzymes. Amikacin is

semisynthetic

aminoglycoside highly resistant to modification by an enzyme that many

bacteria are sensitive to these antibiotics.
Aminoglycoside resistance also appears on the basis of a decrease in
transport activity antimicrobial into a bacterial cell. Aminoglycosides are
not transported into the cells by bacteria Bacteroides species, so
Bacteroides resistant to these antimicrobials. Escherichia coli is also more
resistant to aminoglycosides under anaerobic conditions as in the human
digestive tract.
Resistance Against Chloramphenicol
Majority chloramphenicol resistance caused by the enzymes that add
acetyl groups into antibiotics. Chloramphenicol acetylated will not be
bound to submit the 50S ribosome of bacteria, so it is not able to inhibit
protein sinetsis.
The majority of the resistance to chloramphenicol Yag bacteria containing
plasmids with a gene which encodes chloramphenicol astiltransferase. This
enzyme inactivates chloramphenicol that has passed through the plasma
membrane and enters the cell. Chloramphenicol asetiltransfase produced
constantly by the majority of Gram-negative, but in Staphylococcus
aureus, the synthesis of these enzymes induced by chloramphenicol.
Resistance Against Macrolides

Erythromycin and other macrolide class of antibiotics bound to the 50S

subunit of the bacterial ribosome and block the synthesis potein. In some
cases, resistance to macrolide antibiotics occurs Akiat mutations in
antibiotic targets. The main mechanism of macrolide resistance is based on
metilase RNA enzyme that adds a methyl group added to a specific group
of adenine in the 50S subunit rRNA. Macrolide antibiotics including
eriromisin AKN not bound pad rRNA were methylated.
In Escherichia coli and some strains of other erythromycin-resistant
bacteria, there is a change in the gene encoding the protein L4 or L12
erythromycin on the 50S subunit of bacterial ribosomes, resulting in
decreased affinity of erythromycin on the ribosome. PadaStaphylococcus
aureus, erythromycin resistance due methylated adenine residues in the
23S rRNA.
Fluoroquinolone Resistance Against
Fluorokkuinolon class antibiotics ciprofloxacin and norfloxacin as well as
bound to the subunit of the enzyme DNA gyrase, and blocking the
activity of an enzyme that is essential in maintaining supercoling DNA and
is important in the process of DNA replication. Mutations pda gene
encoding the DNA gyrase cause produced an enzyme that is active but can
not be tied Oleg fluoroquinolone.
Resistance Against Rifampicin
Rifampicin (rifampin) bind to the subunit -RNA polymerase bacteria and
inhibit the function of this enzyme in mRNA transcription. Rifampicin has
an affinity for RNA polymerase of bacteria higher than the
RNApolimerase mammals, so that rifampicin can block mRNA
transcription and protein synthesis in human cells. Resistance to rifampisi
arise from gene mutations in a subunit of RNA polymerase. RNA
polymerase has changed as a result of the mutation function normally, but
can not be inhibited by rifampicin.
Against resitensi Sulphonamides and Trimethoprim
Sulfa drug (sulfonamides) and trimetropin meghambat different reactions
in

the

metabolic

pathway

that

produces

tetrahydrofolate

acid

(tetrahydrofolic acid), which is an essential cofactor in the synthesis of

nucleic acids.
Resistance to sulfonamides and trimethoprim caused by mutations in the
gene encoding an enzyme involved in the metabolic pathway of
tetrahydrofolate acid synthesis. Enzymes changed to function normally but
not inhibited by sulfanaid and trimethoprim.
Prevention resistance can be done using a relatively high dosage of drugs,
exceeding the minimal effective dose and is used in a short time. The use
of a combination of two or more drugs are also ddapat done, for example
in the treatment of tuberculosis, leprosy, cancer. Another means of
prevention is the only limitation antibiotics for severe infections and the
use of the correct dose and according to the rules.
Prevention resistance can be done using a relatively high dosage of drugs,
exceeding the minimal effective dose and is used in a short time. The use
of a combination of two or more drugs can also be done, for example in
the treatment of tuberculosis, leprosy, cancer. Another means of prevention
is the only limitation antibiotics for severe infections and the use of the
correct dose and according to the rules.
Prevention resistance can be done using a relatively high dosage of drugs,
exceeding the minimal effective dose and is used in a short time. The use
of a combination of two leprosy, and cancer. Another means of prevention
is the only limitation antibiotics for severe infections and the use of the
correct dose and according to the rules.
F. Classification of Antibiotics
The classification is based on extensive work activities
a) Substances with a narrow activity (narrow spectrum)
Active substances, especially against one or more types of the
bacteria (gram-positive or gram-negative bacteria only). For
example erythromycin, kanamycin, clindamycin (only against
gram-positive bacteria), streptomycin, gentamicin (only against
gram-negative bacteria only).
b) Substances with broad activity (broad spectrum)

Substances that are efficacious against all types of bacteria both

types of gram-positive bacteria and gram negative. For example,

ampicillin, cephalosporins and chloramphenicol.

The classification is based on the mechanism of action
a) Inhibition of bacterial wall synthesis
b) Inhibiting cell membrane
c) Inhibition of protein synthesis at the ribosome
d) Inhibition of synthetic nucleic acid
e) Metabolic Inhibition (folate antagonist)

Of

each

group

are

working

mechanism,

pharmacokinetics,

pharmacodynamics, as well as antimicrobial activity is different. These

differences lead to differences in the clinical usefulness Because of this
difference is also the mechanism of resistance of each group also experienced
the difference.
The classification is based on his power
a) bactericidal:
Bactericidal antibiotics that are actively disinfect. Included in this group
are

penicillins,

cephalosporins,

aminoglycosides

(large

doses),

cotrimoxazole, polypeptides, rifampicin, isoniazid etc.

b) bacteriostatic:
antibiotics work by preventing or inhibiting the growth of bacteria, do
not kill him, so that disinfection is highly dependent on the immune
system. Included in this group is a sulfonamide, tetracycline,
chloramphenicol, erythromycin, trimetropim, lincomycin, macrolides,
clindamycin, the aminosalicylic acid, etc.
G. Conclusion
Antibiotics are substances produced by microbes, especially fungi
and soil bacteria, which can inhibit the growth or killing microbes.
Antibiotics can also be made synthetically or semisintetis. There are two
kinds of antibiotics are narrow-spectrum and broad spectrum. Where the
effects that are often posed is Resistance. Resistance occurs when the
drug is used at a dose that is too low or less long treatment time. To
prevent resistance to chemotherapy is recommended to use the right dose
or by using a combination of drugs. The classification is based on their

usefulness can be divided into bactericidal and bacteriostatic. Where that

belonged bakterisid are penicillins, cephalosporins, aminoglycosides
(large doses), cotrimoxazole, polypeptides, rifampicin, isoniazid. And
which belonged to the bacteriostatic is a sulfonamide, tetracycline,
chloramphenicol, erythromycin, trimetropim, lincomycin, macrolides,
clindamycin, the aminosalicylic acid.
H. References
Munaf,sjamsuir. 1994. Catatan kuliah farmakologi. Jakarta: EGC
Rang,H.P. 1999. Pharmacology. London: churchill livingstone
Pratiwi, Sylvia T. 2008. Mikrobiologi farmasi. Jakarta: Erlangga