ANTIBIOTIC

What do we need to know about an antibiotic

agent
What is it? Chemical structure
Natural or synthetic product

What does it do? Target site

Mechanisms of action

Where does it go? Absorption, distribution, metabolisme

(and therefore preferred route of and excretion of the drug in the body of
administration) the host
When is it used? Spectrum of activity and important clinical
uses

What are the problem? Toxicity to the human host

Resistance of bacteria

How much does it cost? Great variation between agents but cost is
a serious limitation on availability of some
agents in developing countries

Mims, Medical Microbiology 2005

 Terms in Chemotherapy

 Kemoterapi : penggunaan obat-obatan untuk

mengobati penyakit.
 Antimikroba: obat yang digunakan untuk mengobati
penyakit menular karena bakteri, virus atau jamur.
 Antibiotik: zat yang dihasilkan oleh beberapa
mikroba yang menghambat atau membunuh
mikroba/bakteri lain
 Obat sintetis: senyawa antimikroba yang disintesis
di laboratorium.
3
 What are antibiotics?

Obat yang membunuh atau menghambat

pertumbuhan bakteri tanpa
mempengaruhi kita
• menyerang proses sel prokariotik
• tidak mempengaruhi sel eukariotik
• manusia, jamur, parasit
• tidak mempengaruhi virus
 ANTIBIOTICS
USAGE
Therapy

A
c
Toxicity t Activity
i
v
i
t
y
Pharmacokinetics Resistance
R
e
Host s Commensals
i
s
Host resistance t Colonisation resistance
a
n
Virulence c Colonisation
e

Pathogens
 An ideal antibiotics
Ideal antibiotic
 Tutupi agen penyebab
 Tidak menimbulkan resistensi
 Toksisitas selektif, efek samping
rendah
 Mempertahankan flora mikroba
normal
 Obat harus menembus jaringan tubuh
untuk mencapai bakteri.

For lecture only BC Yang

 Ways of Classifying antibacterial agents

Ada 3 cara mengklasifikasikan agen antibakteri:

Spektrum antibiotik, - apakah bersifat bakterisidal atau

bakteriostatik

Menurut situs target

Dengan struktur kimia

Spektrum antibiotik  adalah istilah yang digunakan untuk
menyampaikan kesan kisaran bakteri yang akan diobati oleh
suatu obat.
Spektrum sempit : jika ada hanya efektif terhadap satu golongan
bakteri.
Spektrum luas: ada yang efektif terhadap berbagai bakteri.
Spektrum yang diperluas: jika agen spektrum sempit dimodifikasi
secara kimia (seperti dalam penambahan rantai samping
baru) & senyawa baru efektif melawan lebih banyak serangga
daripada senyawa induk. Misalnya. : Cephalosporin generasi
ke-2 dimodifikasi menjadi Cephalosporin generasi ke-3 ( =
Cephalosporin spektrum yang diperluas
Antimicrobial action
a. Obat dapat membunuh atau menghambat
pertumbuhan bakteri
Menghambat = bakteriostatik
Membunuh = bakteriosidal
Obat bakteriostatik mengandalkan kekebalan
inang untuk menghilangkan patogen
Obat bakteriosidal berguna dalam situasi ketika
pertahanan inang tidak dapat diandalkan
untuk mengendalikan patogen
• Konsentrasi Hambat Minimum (MIC)
• Konsentrasi terendah antibiotik yang
menghambat pertumbuhan bakteri setelah 16-20
jam inkubasi.
• Konsentrasi Bakterisida Minimum.
• Konsentrasi terendah antibiotik yang dibutuhkan
untuk membunuh 99,9% pertumbuhan bakteri
setelah paparan 16-20 jam.
 MIC and MBC

• Bactericidal : jika MBC sama dengan atau tidak

lebih dari 4 kali lipat lebih tinggi dari MIC.
• Bakteriostatik : jika MBC lebih besar dari 4-8
kali lipat MIC
• Toleransi: jika MBC jauh lebih tinggi dari MIC
• (32 kali lipat lebih tinggi dari MIC)
 Antimicrobial action

• Bakteriostatik vs Bakterisida.
• Untuk sebagian besar infeksi,
keduanya memiliki tingkat yang sama.
Bakterisidal bermanfaat pada infeksi
tertentu (endokarditis, meningitis,
pasien dengan gangguan imun)
 Target site
Ada empat situs target utama untuk
tindakan antimikroba:
Sintesis dinding sel
Sintesis protein
Sintesis asam nukleat & asam folat
Fungsi membran sel
 Modes of action

Penghambatan sintesis dinding sel

bakteri
Bertindak langsung pada membran sel,
permeabilitas, kebocoran
Penghambatan sintesis protein
Penghambatan asam nukleat (DNA
girase, RNA polimerase)
Penghambat metabolit ( penghambatan
metabolisme asam folat)
 Modes of Action

Primary target sites of antimicrobial drugs in bacterial cells.

15
 Modes of action (1)

 Inhibitors of cell wall synthesis.

Penicillins, cephalosporin, bacitracin,
carbapenems and vancomycin, daptomycin,
polymixin.

For lecture only BC Yang

 Building the bacterial cell wall

The linking together of NAG and NAM subunits is facilitated

by several enzymes.
Cell wall construction mechanisms are targets for
antibiotics.
There are three phases of peptidoglycan assembly of a new
wall which can be inhibited by antibiotics
◦ Cytoplasmic phase: build precursor subunits (fosfomycin,
vancomycin)
◦ Membrane-associated phase: transport precursors to the
extracellular space (bacitracin)
◦ Extra-cytoplasmic phase: Cross-link the precursors via
transpeptidases (penicillin, cephalorins)
 -Lactam Characteristics
 Mech OfAction: All inhibit cell wall
synthesis
 Bactericidal (exception: Enterococcus)
 Time-dependent killers
 Short t1/2
 Primarily renally eliminated (exceptions:
nafcillin, oxacillin, ceftriaxone)
 Resistance: β-lactamase degradation
PBP alteration
Decreased penetration
 Penicillin
 Inhibits formation of tetrapeptide side chains
 Cephalosporins by Generation
1st 2nd Generation 3rd Generation 4th
Generation Generation
Cefadroxil 1 Cefaclor1 Cefdinir 1 Cefepime2
Cefprozil1 Cefixime1
Cephalexin 1

Cefuroxime axetil1 Cefpodoxime1

Cefazolin
Cefotetan3 Ceftibuten1
Cefoxitin3 Ceftazidime2
Cefuroxime sodium Cefotaxime
Ceftriaxone

Oral dosage form available

1 3
Anaerobe coverage
Antipseudomonal activity notable
2
 1st Generation Cephalosporins
Best activity against gram-positive aerobes,
with limited activity against gram-negative
aerobes

Gram-positive Gram-negative
MSSA E. coli
Pen-Susp S. pneumoniae K. pneumoniae
Group Streptococci P. mirabilis
Viridans Streptococci
 2nd Generation Cephalosporins

Slightly less active against gram-positive aerobes,

but more active against gram-negative aerobes
Several have activity against anaerobes
Gram-positive Gram-negative
MSSA E. coli
Pen-susp S. pneumoniae K. pneumoniae
Group Streptococci P. mirabilis
Viridans Streptococci H. influenzae
M. catarrhalis
Neisseria spp.
 3rd Generation Cephalosporins
Spectrum of Activity

• Less active against gram-positive aerobes, but

have greater activity against gram-negative
aerobes
• Ceftriaxone and cefotaxime have the best activity
against gram-positive aerobes, including PCN-
resistant S. pneumoniae
• Strong inducers of ESBL production
 3rd Generation Cephalosporins
Spectrum of Activity

Gram-negative aerobes
E. coli K. pneumoniae
P. mirabilis H. influenzae
M. catarrhalis N. gonorrhoeae
N. meningitidis
Citrobacter spp. Enterobacter spp.
Acinetobacter sp. Morganella morganii
Serratia marcescens Providential
Ceftazidime only: Pseudomonas aeruginosa
 4th Generation Cephalosporins
• Extended spectrum of activity
– Gram-positives: similar to ceftriaxone
– Gram-negatives: similar to ceftazidime (including
Pseudomonas aeruginosa), also covers beta-
lactamase producing Enterobacter spp.
• Stable against -lactamases
• Poor inducer of ESBLs
 Carbapenems
(Imipenem, Meropenem, Ertapenem, Doripenem)

• Most broad spectrum activity amongst all

antimicrobials: gram-positive & gram-negative aerobes
& anaerobes
• Meropenem /Imipenem and Doripenem cover P.
aeruginosa
• Ertapenem does NOT cover P. aeruginosa
• Bacteria not covered by carbapenems:
MRSA Staph. epidermidis
VRE C. difficile
 Monobactams
(Aztreonam)

Gram-negatives
E. coli K. pneumoniae
P. mirabilis S. marcescens
H. influenzae M. catarrhalis
Enterobacter Citrobacter
Providencia Morganella
Salmonella Shigella
Pseudomonas aeruginosa

No activity against gram-positives or

anaerobes
 Polymixin

• Inhibit the function of cell membrane.

• Colistin sulfate / Polymixin B : oral for bowel
decontamination , and topical use.
• Colistin methatesulfate (CMS): IV or inhalation
• Mode of action : Diamino butyric acid in polymixin have >>
affinity for LPS in GNB →permeability >> : leakage of cell
contain→ bacterial cell death.
Polymixin not active against :
• Pseudomonas mallei
• Burkholderia cepacia
• Proteus spp, Providentia spp, Serratia spp, Edwardsiella spp,
Brucella spp.
• Gram Pos & Gram Neg aerob cocci.
• Gram Pos aerobic bacilli.
• All Anaerob – Fungi & parasites.
 Vancomycin

Vancomycin was discovered in a soil sample sent to the

pharmaceutical company Eli Lilly by a missionary in Borneo in
the 1950’s.
 Mechanism of Action of Vancomycin

Vancomycin binds to the D-alanyl-D-alanine dipeptide on the peptide side chain of

newly synthesized peptidoglycan subunits, preventing them from being
incorporated into the cell wall by penicillin-binding proteins (PBPs). In many
vancomycin-resistant strains of enterococci, the D-alanyl-D-alanine dipeptide is
replaced with D-alanyl-D-lactate, which is not recognized by vancomycin. Thus, the
peptidoglycan subunit is appropriately incorporated into the cell wall.
 Vancomycin Uses

• Vancomycin is used to treat aerobic Gram + bacteria, including

MRSA and strains of penicillin-resistant Streptococcus
pneumoniae
• Vancomycin is most often administered intravenously
• Vancomycin can also be used to treat anearobic Gram + bacteria,
including Clostridium difficile (in the case of a GI infection,
Vancomycin can be administered orally).
• Vancomycin cannot be used to treat Gram – bacteria, since the
large size of the vancomycin molecule prohibits its passing of the
outer membrane.
 Vancomycin Resistance

• Some Enterococci have developed resistance to

vancomycin (Enterococcus faecium and Enterococcus
faecalis).
• These bacteria are called Vancomycin Resistant
Enterococci (VRE)
Antimicrobial Activity of Vancomycin
Gram-positive Staphylococcus aureus,
bacteria Staphylococcus epidermidis,
Streptococcus pyogenes. Viridans
group streptococci, Streptococcus
pneumoniae, Some enterococci.

Gram-negative
bacteria

Anaerobic bacteria Clostridium spp. Other Gram-

positive anaerobes.

Atypical bacteria
 Modes of action (2)

 Inhibitors of Protein Synthesis.

Aminoglycosides - Streptomycin, gentamicin,
neomycin and kanamycin.
Tetracyclines - Chlortetracycline,
Aminoglycosides oxytetracycline, doxycycline and minocycline.
Erythromycin, lincomycin, chloramphenicol
and clindamycin.

Tetracyclines

For lecture only BC Yang

Antibiotics that inhibit protein synthesis
 The Aminoglycosides include Streptomycin, Gentamicin,
Tobramycin, and Amikacin (all parenteral), as well as Neomycin
(topical, oral).
 Aminoglycoside Mechanism of Action

• Aminoglycosides bind to the 30S subunit of the

bacterial ribosome, thereby inhibiting bacterial
protein synthesis (translation)
 Aminoglycosides

Streptomycin

Streptomycin was the first aminoglycoside to be discovered

(1944) and it still valuable (in combination with other
antibacterial agents) in the treatment of multidrug resistant
tuberculosis (although not a first line drug for tuberculosis)
 Gentamicin
• Gentamicin is most commonly used of the aminoglycosides
• Active against aerobic Gram-negative infections (and
sometimes Gram positive)
• Can be used synergistically, together with a cell wall targeting
agent (e.g. a penicillin)
• Available in parenteral, opthalmic, and topical formulations
 Aminoglycosides

Tobramycin

• Tobramycin has better activity against Pseudomonas

aeruginosa than does gentamicin
• Tobramycin may be given either intramuscularly or
intravenously
• It is also administered by inhaler, particularly useful for
individuals with cystic fibrosis (frequently contract P.
aeruginosa infections)
 Amikacin

• Amikacin has the broadest antimicrobial spectrum of the

aminoglycosides
• It is more resistant to aminoglycoside-inactivating enzymes than
the other aminoglycosides
• It is often used in hospitals where gentamicin- and tobramycin-
resistant microorganisms are prevalent
 Neomycin

Neomycin is widely used for topical administration

Like other aminoglycosides, it is not absorbed well orally, and
is used to prepare the bowel for surgery.
The Aminoglycosides include Streptomycin, Gentamicin, Tobramycin, and
Amikacin (all parenteral), as well as Neomycin (oral).

Gram-positive Used synergistically against

bacteria some: Staphylococci,
Streptococci, Enterococci, and
Listeria monocytogenes
Gram-negative Haemophilus influenzae,
bacteria Enterobacteiaceae,
Pseudomonas aeruginosa

Anaerobic
bacteria

Atypical bacteria

Mycobacteria Mycobacterium tuberculosis,

Mycobacterium avium complex.
 Uses of Aminoglycoside Antibiotics

• Unlike vancomycin, the aminoglycosides have

excellent activity against Gram – aerobic bacteria
• Their extensive positive charge enables them to bind
to and penetrate the negatively charged outer
membrane and get into the periplasm
• They are further transported into the cytoplasm by a
bacterial transport system.
Macrolides and Ketolides

The structures of erythromycin and

telithromycin Circled substituents
and distinguish telithromycin from
the macrolides.
 Mechanism of Action of Macrolide Antibiotics

• Macrolides bind tightly to the 50S subunit of the bacterial

ribosome, thus blocking the exit of the newly synthesized
peptide
• Thus, they are interfering with bacterial translation
 Uses of Macrolide Antibiotics

• Active against a broad range of bacteria

• Effective against some stphylococci and
streptococci, but not usually used for MRSA or
penicillin-resistant streptococci
• Most aerobic Gram neg bacteria are resistant
• Active against many atypical bacteria and
some mycobacteria and spirochetes
The macrolide group consists of Erythromycin, Clarithromycin, and Azithromycin (all
oral, with erythromycin and azithromycin also being available parenterally).

Gram-positive Some Streptococcus pyogenes. Some

bacteria viridans streptococci, Some
Streptococcus pneumoniae. Some
Staphylococcus aureus.
Gram-negative Neiseria spp. Some Haemophilus
bacteria influenzae. Bordetella pertussis

Anaerobic
bacteria
Atypical Chlamydia spp. Mycoplasma spp.
bacteria Legionella pneumophila, Some
Rickettsia spp.
Mycobacteria Mycobacterium avium complex,
Mycobacterium leprae.
Spirochetes Treponema pallidum, Borrelia
burgdorferi.
 Mechanism of Action of the Tetracycline
Antibiotics
• The tetracyclines bind to the 30S subunit of
the bacterial ribosome and prevent binding by
tRNA molecules loaded with amino acids.
 Uses of the Tetracycline Antibiotics

• Main use is against atypical bacteria, including

rickettsiae, chlamydiae, and mycoplasmas
• Also active agains some aerobic Gram-positive
pathogens and some aerobic Gram-negative
bacteria
The Tetracycline Class of Antibiotics consists of Doxycycline and
Tigecycline (parenteral) as well as Tetracycline, Doxycycline and
Minocycline (oral)

Gram-positive Some Streptococcus pneumoniae

bacteria

Gram-negative Haemophilus influenzae,

bacteria Neisseria meningitidis

Anaerobic Some Clostridia spp. Borrelia

bacteria burgdorferi, Treponema pallidum

Atypical bacteria Rickettsia spp. Chlamydia spp.

Tigecycline
The antimicrobial activity of Tigecycline (parenteral)

Gram-positive Streptococcus pyogenes.

bacteria Viridans group streptococci,
Streptococcus pneumoniae,
Staphylococci, Enterococci,
Listeria monocytogenes
Gram-negative Haemophilus influenzae,
bacteria Neisseria spp.
Enterobacteriaceae

Anaerobic Bacteroides fragilis, Many other

bacteria anaerobes

Atypical bacteria Mycoplasma spp.

Clindamycin
 Mechanism of Action of Clindamycin

• Clindamycin binds to the 50S subunit of the

ribosome to inhibit protein synthesis
 Uses of Clindamycin

• Clindamycin is a member of the lincosamide series of

antibiotics
• Main utility is in treatment of Gram-positive bacteria and
anaerobic bacteria
• Active against staphylococcus, including some strains of MRSA
• Not useful against Gram-negative bacteria
 Toxicity of Clindamycin

Clindamycin kills many

components of the
gastrointestinal flora,
leaving only Clostridium
difficile
This can result in
overgrowth by C. difficile,
which is resistant
The Antimicrobial Activity of Clindamycin (both oral and
parenteral)

Gram-positive Some Streptococcus pyogenes,

bacteria Some viridans group streptococci.
Some Streptococcus
pneumoniae, Some
Staphylococcus aureus
Gram-negative
bacteria

Anaerobic Some Bacteroides fragilis, Some

bacteria Clostridium spp. Most other
anaerobes.

Atypical bacteria
Chloramphenicol
 Mechanism of Action of Chloroamphenicol

• Binds to the 50S subunit of the bacterial

ribosome, where it blocks binding of tRNA
 Uses of Chloramphenicol

• Severe toxicity limits utility

• The most serious side effect of chloramphenicol
treatment is aplastic anaemia (a condition where
bone marrow does not produce sufficient new cells
to replenish blood cells)
• This effect is rare and is generally fatal: there is no
treatment and there is no way of predicting who may
or may not get this side effect.
• The effect usually occurs weeks or months after
chloramphenicol treatment has been stopped.
 Uses of Chloramphenicol

• However, despite its toxicity, chloramphenicol

has a wide spectrum of activity, that includes
many aerobic Gram-positive, Gram-negative,
anaerobic, and atypical bacteria
The Antimicrobial Activity of Chloramphenicol

Gram-positive Streptococcus pyogenes,

bacteria Viridans group streptococci.
Some Streptococcus pneumoniae

Gram-negative Haemophilus influenzae,

bacteria Neisseria spp. Salmonella spp.
Shigella spp.

Anaerobic Bacteroides fragilis. Some

bacteria Clostridia spp. Other anaerobic
Gram-positive and Gram negative
bacteria
Atypical bacteria Rickettsia spp. Chlamydia
trachomatis, Mycoplasma spp.
 Modes of action (3)

 Inhibitors of metabolites
(Antimetabolites).
Sulfonamides - Sulfanilamide, sulfadiazine silver
and sulfamethoxazole.
Trimethoprim, ethambutol, isoniazid.

For lecture only BC Yang

 The Sulfa Drugs
• Most commonly used sulfa drug is a mixture of the sulfa drug
Sulfamethoxazole and Trimethoprim
• These two drugs work in synergy, with the combination being superior to
either drug alone.

Sulfamethoxazole Trimethoprim
• This combination is known as co-trimoxazole, TMP-
sulfa, or TMP-SMX
 Mechanism of Activity of Sulfa Drugs

• Trimethoprim-sulfamethoxazole works by
preventing the synthesis of tetrahydrofolate
(THF), an essential cofactor for the metabolic
pathways that generate deoxynucleotides, the
building blocks of DNA.
 Tetrahydrofolic Acid Biosynthetic Pathway

• In the first step of the pathway, the sulfonamides are mistaken for the
natural substrate, p-aminobenzoic acid (PABA) and the drug acts as a
competitive inhibitor of this enzyme
• In a later step, the trimethoprim acts as a structural analog of dihydrofolate
and therefore inhibits dihydrofolate reductase
Another sulfa drug is Dapsone, which is used to
treat Mycobacterium leprae

Dapsone
The Antimicrobial Activity of the Sulfa Drugs

Gram-positive Some Sreptococcus pneumoniae,

bacteria Some Staphylococci, Listeria
monocytogenes

Gram-negative Some Haemophilus influenzae,

bacteria Some Enterobacteriaceae

Anaerobic
bacteria

Atypical bacteria

Mycobacteria Mycobacterium leprae

(Dapsone)
 Modes of action (4)
 Inhibitors of nucleic
acids (DNA/RNA
polymerase).
Quinolones - Nalidixic acid,
norfloxacin and ciprofloxacin.
Rifamycin and flucytosine. 

For lecture only BC Yang

 Antibiotics that inhibit nucleic acid synthesis

• Fluoroquinolones
– Interferes with function of topoisomerase
• Rifamycins
– Blocks prokaryotic RNA polymerase from initiating
transcription
Fluoroquinolones
 Mechanism of Action: Quinolones

• Quinolone antibiotics inhibit bacterial DNA

gyrase (Gram negative bacteria) or
Topoisomerase IV (Gram positive bacteria)
 Uses of the Quinolone Antibiotics

• Urinary Tract Infections: fluoroquinolones are

more effective than trimethoprim-
sulfamethoxazole
• Prostatitis
• Respiratory tract infections
• Gastrointestinal and Abdominal Infections
Antimicrobial Activity of the Quinolones (oral)

Gram-positive Some Staphylococcus aureus,

bacteria Streptococcus pyogenes, Virdans
group streptococci,
Streptococcus pneumoniae
Gram-negative Neisseria spp. Haemophilus
bacteria influenzae
Many Enterobacteriaceae, Some
Pseudomonas aeruginosa
Anaerobic Some clostridia spp, Some
bacteria Bacteroides spp.
Atypical bacteria Chlamydia and Chlamydophilia,
Mycoplasma pneumoniae,
Legionella spp

Mycobacteria Mycobacterium tuberculosis,

Mycobacterium avium complex,
Mycobacterium leprae
 Metronidazole (Flagyl)

Metronidazole is used in the treatment of infections

caused by anaerobic bacteria
 Metronidazole Mechanism of Action
Metronidazole is a prodrug. It is converted in anaerobic organisms by the redox
enzyme pyruvate-ferredoxin oxidoreductase. The nitro group of metronidazole is
chemically reduced by ferredoxin (or a ferredoxin-linked metabolic process) and the
products are responsible for disrupting the DNA helical structure, thus inhibiting
nucleic acid synthesis.
 Mechanism of Action of Metronidazole

 Metronidazole is selectively taken up by

anaerobic bacteria and sensitive protozoal
organisms because of the ability of these
organisms to reduce metronidazole to its
active form intracellularly.
Systemic metronidazole is indicated for the treatment of:
 Vaginitis due to Trichomonas vaginalis (protozoal) infection in both symptomatic
patients as well as their asymptomatic sexual contacts;

 Pelvic inflammatory disease in conjunction with other antibiotics such as ofloxacin,

levofloxacin, or ceftriaxone

 Protozoal infections due to Entamoeba histolytica (Amoebic dysentery or Hepatic

abscesses), and Giardia lamblia (Giardiasis) should be treated alone or in conjunction
with iodoquinol or diloxanide furoate

 Anaerobic bacterial infections such as Bacteroides fragilis, spp, Fusobacterium spp,

Clostridium spp, Peptostreptococcus spp, Prevotella spp, or any other anaerobes in
intraabdominal abscess, peritonitis, empyema, pneumonia, aspiration pneumonia, lung
abscess, diabetic foot ulcer, meningitis and brain abscess, bone and joint infections,
septicemia, endometritis, tubo-ovarian abscess, or endocarditis

 Pseudomembranous colitis due to Clostridium difficile

 Helicobacter pylori eradication therapy, as part of a multi-drug regimen in peptic ulcer

disease

 Prophylaxis for those undergoing potentially contaminated colorectal surgery and may
be combined with neomycin
Antimicrobial Activity of Metronidazole (both oral and
intravenous)

Gram-positive
bacteria

Gram-negative
bacteria

Anaerobic Bacteroides fragilis, Clostridium

bacteria spp. Most other anaerobes

Atypical bacteria
 Rifamycins

• Rifampin is the oldest and most widely used of the

rifamycins
• Rifampin is also the most potent inducer of the
cytochrome P450 system
•
 Mechanism of Action of Rifampin

• Rifampin inhibits transcription by inactivating

bacterial RNA polymerase
Overview of anti-mycobacterial drugs
 Factors for optimal antibiotic action
 pH of environment:
 Nitrofurantoin is more active in acid pH; sulfonamides and
aminoglycoside are more active in alkaline pH.
 Components of environment:
 Serum proteins bind to penicillin in varying degrees.
 Stability of drug:
 Aminoglycosides and chloramphenical are stable for long
period in vivo.
 Size of inoculums:
The larger the bacterial inoculum, the greater the chance for
resistant mutant to emerge.
 Metablic activity of microorganisms:
Actively and rapidly growing organisms are more susceptible
to drug action

For lecture only BC Yang

  Abscess: circulation is blocked off.

 Foreign bodies, invasive medical equipment,

prothesa: obstruction of the urinary, biliary;
ventilator, catheters .

 Immunity, the most important defence

mechanism in vivo and enhance the efficacy of
antimicrobial action.

For lecture only BC Yang

What are 3 basic ways antimicrobial
therapy is used?

• Empiric therapy
– Initiation of treatment prior to determination of a
firm diagnosis
• Definitive therapy
– Organism and susceptibilities are known
• Prophylaxis
– Prevent initial or recurrent infection
 EMPIRIC ANTIBIOTIC THERAPY
Based on:
- Epidemiologic data on the expected pathogen and
its prevailing ABx susceptibility which may have
significant geographical variation
- Directing coverage against the most likely
pathogen.
→ Educated / scientific guess
If a patient is severely ill/ threathening life, initiated
IV → then de-escalation tx → PO switch tx
Culture of appropriate clinical specimens should be
obtained prior to starting empiric tx
 Definitive antibiotic therapy

• Should be based on the isolated etiologic

agent and its susceptibility against
antibiotics.
• Administered to cure the existing or
suspected bacterial infection.
 Prophylactic antibiotic

I. Medical prophylaxis to prevent from certain

infections:
- long-term use of penicillin for individual who had
a splenectomy.
- reduces the possibility of overhelming infection
with pneumo / meningo-coccus.
- who are at risk of developing endocarditis before
any invasive procedure
- Recurrent UTI
II. Surgical antimicrobial prophylaxis
- Surgical wounds infections are substantially
reduced by giving prophylactic antibiotics,
which would be effective against the most
common pathogens resposible for infection in
the type of surgery being used.
- Continuation of prophylaxis for more than 24-
48 hour is not advised.
Principles of Antimicrobial Use

Patient with Symptoms &Signs

Empiric Use +Culture &Antibiotic

Susceptibility Test (AST)

Pathogen Directed
Result of
culture & AST
Narrowest Spectrum

Best Outcome