ANTIBIOTIK

DEPARTEMEN FARMAKOLOGI KLNIK

FK UNISSULA
History of Antimicrobials
• 1600s
–Quinine for malaria
–Emetine for amebiasis (Entamoeba histolytica)
• 1900-1910
–Arsphenamines for syphilis
• 1935
–Sulfonamides - broadly active
• 1940
–Penicillin - substantially more active than sulfa drugs
–Originally discovered in 1929 by Alexander Fleming (Scottish)
• Nobel Prize, 1945
• Knighted, 1944
–Produced by fungus Penicillium chrysogenum
Cara masuk
•kuman patogen dapat masuk melalui kulit rusak,
atau oleh konsumsi, inhalasi, atau kontak
dengan selaput lendir seperti hidung, kencing,
atau mukosa vagina
•Kemampuan microba dalam menimbulkan
penyakit tergantung dari beberapa hal:
- imunitas host
- virulensi
Jenis
1. Pewarnaan
- gram negatif
- gram positif
2. Bentuk
- batang
- spiral
- sferis
3. Kemampuan menggunakan O2
- anaerob
- aerob
 PENGGOLONGAN ANTIBIOTIK
BERDASARKAN MEKANISME AKSI

1. Cell Wall
2. Cell membrane
3. Protein synthesis
4. Nucleic Acid Synthesis
5. Antimetabolites
 Spectrum of Activity
• Range of microorganisms that are affected by agent
– Broad spectrum
• Wide range, e.g. both gram-pos & gram-neg
• Used when infective bacterial agent on is not precisely
identified
– Narrow spectrum
• Limited number, or specific group of bacteria
• Used to prevent development of resistance
• Less of an affect on normal bacterial flora
Antibiotic Spectrum

Obligate intracellular microorganisms

Chlamydia – tiny, non-motile, spherical bacteria
Rickettsia – small, non-motile, gram-negative bacteria
• Tujuan utama pemberian antibiotik adalah untuk
membantu pertahanan tubuh melawan microba
pathogen
• Anti microba yang kerjanya mematikan microba
bakteriosidal
• Anti microba yang kerjanya mengurangi pertumbuhan
bakteri bakteriostatik
Prinsip Dasar Penggunaan Antibiotik Terapi:
• Terapi Empiris : Guidelines, pola kuman
• Terapi Definitif : sesuai hasil kultur
Langkah pemilihan antibiotic (definitif)
•Px lab( darah, urin, feses, sputum, cairan
spinal, sekret)identifikasi
kumanIdentifikasi kuman test
sensitivitas antibiotik
•Cultur and sensitivity (C&S testing)
•Pemeriksaan diatas membutuhkan waktu,
sedangkan proses terus berjalan broad
spectrum antibiotik
• Beberapa kasus penggunaan antibiotik secara single
drug (jika kombinasi akan menurunkan efikasi
antagonisme)
• Contoh penggunaan antibiotik kombinasi pada kasus TB
paru
• Salah satu efek merugikan penngunaan antibiotik
superinfeksi/sekunder infeksi flora normal yang ada di
organ mati pertumbuhan kuman pathogen akan
meningkat.
• Flora normal non spesifik imunologi
• Infeksi opotunistik flora normal menjadi pathogen oleh
karena imun turun
Faktor Host
•Kekebalan host
sistem kekebalan host dibutuhkan dalam
membantu antibiotik untuk
membunuh/mengurangi pertumbuhan kuman
•Kondisi jaringan
vaskularisasi menentukan tingkat efektivitas
pengobatan
Perhatian
•Riwayat alergi obat
innitial assesment riwayat obat yang
diminum, reaksi alergi??deskripsikan
alergi salah satu antibiotik usahakan tidak
memilih antibiotik yang segolongan
•Kondisi lain
usia, kehamilan,genetik
Beta lactam
 Beta lactams

penicillins cephalosporins carbapenems monobactams

Natural Imipenem aztreona
penicillins Meropene m
Penicillin G m
Penicillin V Ertapenem
Benzathine P
Procaine P
Methicilli
Penicillinase R
Nafcillin
n 1st gen 2nd gen 3rd gen 4th gen 5th gen
Cloxacilli
aminopenicillins Cefadroxil Cefaclor Cefotaxime cefepim Ceftaroline
n
Amoxycillin Cephalexin Cefamandol Ceftazidim e ceftobiprol
ampicillin Cephradin e e e
Extended e cefazolin Cefuroxime ceftriaxone
spectrum cefoxitin
Ticarcilin
Piperacilin
carbenicillin
Penicillin
•was originally extracted from the mould
Penicillium notatum.
•Penicillin consists of thiazolidine ring fused
with a beta lactam ring which is essential
for its antibacterial activity.
 Cell Wall

penicillin

• Penicillin has a 4-member ring

• “looks like” part of the cell wall to the cross-linking enzyme
• Penicillin competes with the normal cell wall component for the
cross-linking enzyme, i.e. competitive inhibition
• Prevents this enzyme from cross-linking cell wall
Beta Lactams Against Bacterial Cell
Wall
Cell wall

Osmotic
Pressure

Cell Membrane

Antibiotic against cell wall

Osmotic
Pressure
Cell membrane
Rupture
Mechanism of Action
•The bacterial cell wall is a rigid outerlayer
that completely surrounds the cytoplasmic
membrane.
•Penicillin and other betalactam antibiotics
inhibit bacterial growth by interfering with
a specific step in bacterial cell wall
synthesis
•Penicillin is effective against gram positive and
negative cocci and some gram positive bacilli.
Among the cocci, streptococci are highly
sensitive.
• Gonococci, pneumococci and meningococci are
sensitive to penicillin.
•Among the bacilli gram positive: Bacillus
anthracis, Corynebacterium diphtheriae,
Clostridium species are highly sensitive.
Among the spirochetes, Treponema pallidum is
highly sensitive to penicillin.
•Gram negative bacilli, fungi,
protozoa,rickettsiae, chlamydiae, viruses and
Mycobacterium tuberculosis are totally
insensitive to penicillin.
Pharmacokinetic
•Setelah masuk PO benzyl penisillin akan rusak
di lambung absorbsi di duodenum
•Absorbsi cepat lewat IM, IV lewat cairan
tubuh
•Dalam darah terikat oleh protein albumin
•Cepat di dikeluarkan lewat ginjal urin (porsi
besar)
Adverese effect
• Penisillin obat non toxic dan tergolong aman
• 5-10% reaksi hypesensitivitas, syok anafilaksis
• Efek minor: nausea, vomiting, pain, inflamasi di
daerah suntikan.
• Efek samping mayor adalah allergic reactions and
anaphylaxis  skin rash, pruritus, serum sickness like
syndrome, eosinophilia, angioneurotic edema,
asthma, haematuria, albuminuria, haemolytic anemia,
granulocytopenia and anaphylaxis
CEPHALOSPORINS
•Cephalosporins are important bactericidal broad
spectrum β-lactam antibiotics used for the
treatment of septicaemia, pneumonia,
meningitis, urinary tract infections, peritonitis
and biliary tract infections.
•They are obtained from fungus Cephalosporium
acremonium and are chemically related to
penicillin
• It consists of beta lactam ring fused to a
dihydrothiazine ring.
• All cephalosporins act by inhibiting bacterial cell wall
synthesis and are bactericidal. Also the autolytic
enzymes in cell wall may be activated leading to
bacterial death.
• They are widely distributed after administration
throughout body fluids.
• Cephalosporins are mainly excreted by the kidneys
and dose should be altered in patients with renal
disease
Pharmacokinetics
•Cephalosporins are distributed in the body
after oral or parenteral administration in
same manner as penicillin is distributed.
•The majority are not metabolized and are
eliminated by kidney.
Adverse Reactions

•pain at the site of injection and can also cause

thrombophlebitis.
•Allergic reactions ; skin rash, fever, serum
sickness, eosinophilia, neutropenia and rarely
anaphylactic reaction.
•CNS side effects; nystagmus and hallucinations.
•Larger doses can cause nephrotoxicity
Fluoroquinolones
Fluoroquinolones
Quinolone pharmacore
Mechanism of Action

Prevent:
 Relaxation of supercoiled DNA
before replication
 DNA recombination
 DNA repair
 Spectrum of Activity
•Gram-positive
•Gram-Negative (Enterobacteriaceae H.
influenzae, Neisseria sp. Pseudomonas
aeruginosa)
•Ciprofloxacin is most active
•Atypical bacteria: all have excellent
activity
Summary
• Wide range of activity against Gram positive and
negative bacteria.
• Sepsis from Intra-abdominal and Renal Sources
• Coliforms (Gram negative bacilli)
• UTI
• E. coli
• Very good tissue penetration
• Excellent oral bioavailability
• High risk for C.difficile
Aminoglikosida
Aminoglycosides Antibiotic
•Bactericidal antibiotics originally obtained from
various Streptomyces species.
•act by inhibiting protein synthesis of bacteria by
directly combining with ribosomes.
•All aminoglycosides are poorly absorbed after
oral administration, more active in alkaline pH
and excreted unchanged by glomerular filtration
 30S Ribosomal Unit Blockage by
Aminoglycosides

•Causes mRNA decoding errors

•All the aminoglycosides produce cochlear
and vestibular damage (ototoxicity)
•Another serious side effect is
nephrotoxicity.
•reduce the acetylcholine release from the
motor nerve endings  neuromuscular
blockade.
1. STREPTOMYCIN
•The aminoglycoside antibiotic, obtained from
Streptomyces griseus is the first antitubercular
drug.
•its action by combining with bacterial
ribosome and induces misreading of mRNA
codons.
•sensitive bacteria, disruption of cytoplasmic
membrane occurs resulting in leakage of
amino acids, ions, leading to bacterial death
•oral administration it is not absorbed.
•After IM injection the absorption is rapid.
•It is excreted unchanged in urine.
•Half life is prolonged in patients of renal
failure
•Adverse effects include pain at injection site,
ototoxicity, nephrotoxicity, skin rash, fever,
exfoliative dermatitis and eosinophilia.
Anaphylaxis is rarely seen. Optic nerve
dysfunction
•Indication; all forms of tuberculosis along with
other antitubercular drugs, tularemia, plague,
brucellosis, bacterial endocarditis,
entero�coccal endocarditis
2. GENTAMICIN
• It is obtained from Micromonospora pupurea.
• broader spectrum of action and is effective against
Pseudomonas aeruginosa, E. coli, Klebsiella,
Enterobacter and Proteus.
• Indication; Pseudomonas or Proteus infections in
burns, urinary tract infections, lung abscesses,
osteomyelitis, middle ear infection, septicaemia;
meningitis caused by gram negative bacilli,
peritonitis, in skin and soft tissue infections and
postoperative infection.
•Topical administration in the form of drop and
ointment  for the treatment of infected burns,
wounds and the prevention of intravenous
catheter infections and in the treatment of
ocular infections
•Adverse effects include ototoxicity (incidence is
related to dose and duration of therapy)
3.TOBRAMYCIN
•It belongs to family nebramycins, is isolated
from Streptomyces tenebrarius.
•antibacterial activity is similar to
gentamicin and slightly more active than
gentamicin against Pseudomonas
aeruginosa and Proteus.
4.AMIKACIN
•It is semisynthetic derivative of kanamycin.
•It is active against gentamicin resistant
organisms e.g. Pseudomonas aeruginosa,
Klebsiella, E. coli and Proteus.
•It is resistant to bacterial aminoglycoside
inactivating enzymes
5. KANAMYCIN
•It is derived  Streptomyces kanamyceticus.
• It is active against Pseudomonas, but due to
severe ototoxicity and nephrotoxicity, it is
replaced by other aminoglycosides and
occasionally used in multidrug resistant cases of
tuberculosis
5. NEOMYCIN

•It is isolated from Streptomyces fradiae and is

effective against most gram negative bacilli and
some gram positive cocci.
•Because of its high ototoxicity and
nephrotoxicitynot used systemically
•used locally in various skin and eye infections
6.FRAMYCETIN
•It is derived from Streptomyces lavendule.
•It is similar to neomycin and used locally in
various skin infections and eye/ear
infections
Tetracyclines

•Hydronaphthacene nucleus containing four fused rings

•Tetracycline
•Short acting

•Doxycycline
•Long acting
Mechanism of Action

• Inhibit protein synthesis

• Bind reversibly to bacterial 30S ribosomal
subunits
• Prevents polypeptide synthesis
• Bacteriostatic
Spectrum of Activity
• All have similar activities
• Gram positives aerobic cocci and rods
• Staphylococci
• Streptococci
• Gram negative aerobic bacteria
• Atypical organisms
• Mycoplasmas
• Chlamydiae
• Rickettsiae
• Protozoa
Adverse Effects
• Oesophageal ulceration
• Photosensitivity reaction
• Incorporate into foetal and children bone and teeth

Avoid in pregnancy and children

Summary

•Very good tissue penetration

•Use usually limited to;
•Skin and soft tissue infections
•Chlamydia
MACROLIDE ANTIBIOTICS
•their name indicates are characterized
by a large or macrocyclic lactone ring
with attached sugar residue(s).
1. ERYTHROMYCIN

•Erythromycin was isolated from Streptomyces

erythreus.
•widely used antibiotic both in children as well as
in adults.
•It acts by binding with 50S ribosomal subunit of
bacteria and inhibit protein synthesis.
•It is a narrow spectrum antibiotic, low
concentration are bacteriostatic, however high
concentrations are bactericidal
•Erythromycin is effective against gram positive
and few gram negative organisms which mainly
includes pneumococci, streptococci,
staphylococci, Neisseria and some strains of C.
diphtheriae, H. influenzae,Rickettsiae and
Treponema
•Adverse effects ; gastrointestinal side
effects like nausea, epigastric pain are
common. Diarrhoea occurs occasionally.
•Skin rashes, hypersensitivity
reaction,hepatotoxicity, oral candidiasis,
thrombophlebitis and fever have been
reported
•Erythromycin is used as a substitute to
penicillin in allergic patients for upper
respiratory tract infections, e.g.
tonsillitis, pharyngitis and mastoiditis,
pneumococcal infection and
prophylaxis of rheumatic fever.
2. ROXITHROMYCIN

•Roxithromycin is a semisynthetic macrolide

antibiotic
•It is effective against Streptococcusnpyogenes,
Streptococcus viridans, Streptococcus
pneumoniae, Staphylococcus mitis, S. aureus
and coagulase negative staphylococci, Neisseria
meningitidis, Bordetella pertussis,
• Moraxella catarrhalis, Corynebacterium diphtheriae,
Listeria monocytogenes, Clostridium, Mycoplasma
pneumoniae, Pasteurella multocida, Chlamydia
trachomatis/psittaci/pneumoniae, Ureaplasma
urealyticum, Legionella pneumophila, Helicobacter
pylori, Gardnerella vaginalis
• It is more stable in acid media than other macrolides
• Found in the serum after 15 minutes of administration.
It is more than 90% plasma protein bound and more
than half the dose is excreted unchanged in urine and
faeces.
•Adverse effects like other macrolide
generally
•Hypersensitivity reactions like rash,
urticaria, angioedema,exceptionally
bronchospasm, anaphylactic shock; dizzy
sensations (caution in driving or use of
machinery
3. AZITHROMYCIN
• Azithromycin is an azalide antibiotic, a sub-class of the
macrolides.
• Differs chemically from erythromycin in that a methyl
substituted nitrogen atom is incorporated into the
lactone ring.
• Following oral administration, azithromycin is rapidly
absorbed and widely distributed throughout the body
•indication:
1. Lower respiratory tract infections
2. Ear, nose and throat infections like tonsillitis,
sinusitis, otitis media and pharyngitis.
3. Skin/skin structure infections
4. CLARITHROMYCIN
• It is a macrolide antibiotic obtained by substitution
of hydroxyl group by a CH3O group in the
erythromycin lactone ring.
• Found to be 2 to 10 times more active than
erythromycin.
• Clarithromycin is readily and rapidly absorbed after
oral administration and is metabolized significantly in
liver. Active metabolite is excreted by kidney and
other routes
5. CLINDAMYCIN
• It is a lincosamide and act by binding exclusively to 50S
submit of the bacterial ribosomes and hence
suppresses protein synthesis. It is 7-chloro-7-
deoxylincomycin, a semisynthetic derivative of
lincomycin
• It inhibits most of the gram positive cocci e.g.
streptococci, staphylococci and pneumococci, C.
diphtheriae, Actinomyces, Nocardia and Toxoplasma
• Oral absorption is good. It is largely metabolized and
metabolites are excreted in urine and bile.
• Adverse effects include pain at injection site,
stomatitis, glossitis, angioneurotic edema, serum
sickness, vertigo, tinnitus, aplastic anaemia.
Hypotension and cardiac arrest after rapid IV use.
Anorexia, metallic taste, oesophagitis, abdominal pain
• It is used in the treatment of severe anaerobic
infections caused by bacteroides and other anaerobes.
It is also used in combination with aminoglycoside.
6. LINCOMYCIN
• It is mainly bacteriostatic and inhibits the growth of
gram positive organisms which includes
staphylococci, streptococci, pneumococci, C.
diphtheriae and B. anthracis. Like erythromycin it act
by interfering with protein synthesis
• indication; upper and lower respiratory tract
infections, skin infections, septicaemia, bone and
joint infection including acute haematogenous
osteomyelitis
7. VANCOMYCIN

•It is a glycopeptide antibiotic and primarily

active against gram positive bacteria, strains of
Staph. aureus which are resistant to methicillin
are inhibited by vancomycin. It is also effective
against Strep. viridans, enterococcus,
Clostridium difficile and diphtheroids
• It is bactericidal drug and it exerts it action by
inhibiting the synthesis of the cell wall in sensitive
bacteria.
• It is given by parenteral route and high concentration
of drug may accumulate when renal function is
impaired
• Indication; serious life threatening staphylococcal
infections resistant to other antibiotics, in severe
staphylococcal infections in patients who are allergic
to penicillin and cephalosporin
POLYPEPTIDE ANTIBIOTICS

• They have bactericidal activity against gram negative

bacteria only and are low molecular cationic
polypeptide antibiotics
1.POLYMYXIN B
•Has detergent like action on cell membrane and
have high affinity for phospholipids. They
penetrate into and disrupt the structure of cell
membranes, as a result of which amino acids
and ions leak out.
•After oral administration negligible or no
absorption occurs.
• It is used systemically in enteric infections caused by
gram negative organisms
• Topically for pseudomonal infections of conjunctiva and
cornea, burns and skin
2. COLISTIN
• Also known as polymyxin E, is also a cationic detergent
used only orally. Side effects and uses are similar to
polymyxin B.