ANTIMICROBIAL DRUGS

Iwan Dwiprahasto
Department of Pharmacology and Therapy
Faculty of Medicine GMU
Why do young children have more
illness?
Infection can result from sharing towels, dishes, or from
handling contaminated objects. Indirect contact or skin to
skin contact can also result in the spread of an illness.
Sometimes an illness is passed to others by a carrier, or a
person who has been infected by a germ but does not look or
feel sick. This person may carry the germ in their nose, throat,
or stomach. They can pass the germ to others by coughing,
sneezing, or by not washing their hands properly.
 Your hands carry many germs
even if you can’t see them.

Many people don’t wash their

hands because they look clean.

As you can see this is not

Light patches indicate always the case.
germs carried on the
hands
Some examples of contagious bacterial diseases are:

strep throat

Impetigo

pertussis (whooping cough)

bacterial conjunctivitis (pink eye)

Antibiotics Work
Some contagious viral infections include:

varicella (chicken pox)

rubella (German measles)

the common cold

hepatitis

mumps

infectious mononucleosis

rubeola (measles)

Antibiotics Don’t Work

 Antimicrobial therapy
When the balance between the microorganism and the
host tilts in the direction of he microorganism

the bodies normal defenses cannot prevent or overcome

the disease

When this occurs we turn to chemotherapy.

Chemotherapy is the
treatment of disease
with chemicals taken
into the body.
chemotherap
• Drugs for chemotherapy
eutic agents

• Chemotherapeutic agents
antimicrobial
used to treat infectious
drugs diseases are called

they must act within the host

 Terminology
Antimicrobial drugs are chemotherapeutic drugs

Some antimicrobials Some antimicrobials

are synthetic drugs are called antibiotics

they are produced

they are synthesized in
naturally by bacteria
the laboratory.
and fungi.
 Introduction

No effct Infection
Principles of Anti-infective Therapy

Identifying the infecting organism

Having information of its antimicrobial

susceptibility (or potential
susceptibility)

Consider Host factors that will impact

on choice on antimicrobial
The classification of antimicrobial drugs

Antibacterials

Antiviral

Antimicrobials Antifungal

Antiprotozoal

Anthelmintics
 Spectrum of antimicrobial activity

Narrow spectrum Broad spectrum

affect only Gram- affect both Gram-

positive cells or only positive and Gram-
Gram-negative cells negative cells

The normal flora is affected, too.

 Antimicrobial therapy

When the balance between the microorganism and the

host tilts in the direction of he microorganism

the bodies normal defenses cannot prevent or

overcome the disease

we turn to chemotherapy

the treatment of disease with chemicals taken into the body

The following criteria should be used to evaluate
chemotherapeutic agents

It should demonstrate selective toxicity for the

microbe, but not the host (most are actually
somewhat toxic to the host).

It should not produce hypersensitivity reactions

in most hosts

It should penetrate body tissues rapidly and be

retained for an adequate time

Microbes should not readily develop resistance

to it.
 An Ideal Antimicrobial

Quick acting

Few side
Water soluble
effects

Broad
Quick “kill” of
spectrum in
the pathogen
action
 Antimicrobial therapy

The problem with broad spectrum antimicrobials

much of the normal flora of the host is destroyed

may allow certain normal flora which, may be resistant to

the antimicrobic, to flourish and cause an opportunistic
infection

superinfection
 Antimicrobial drugs

bacteriocidal bacteriostatic

kill the bacteria simply prevent the growth

of the bacteria

effective when host the host’s own defenses of

immune system is phagocytosis and antibody
compromised production will destroy the
bacteria
No Tetracycline
antimicrobial Fucidic acid
agent Sulfonamida
Chloramphenicol
PAS
Lincomycin
Erithromycin (Low conc)
Bacteriostatic Clindamycin

Penicillin
Aminoglycosides
Cephalosporin
Bactericidal
Cotrimoxazol
Isoniazid
Rifampicin
Erithromycin (high conc)
Vankomisin
 Antibiotic susceptiility testing (in vitro)

Minimum inhibitory concentration (MIC)

Lowest concentration that results in

inhibition of visible growth

Minimum bactericidal concentration (MBC)

Lowest concentration that kills 99.9% of

the original inoculum
How antimicrobials act?
Peptidoglycan synthesis
Fig. 13-2

Antibiotics classification
Resistance to beta lactams - Gram-negative bacteria
Cross-linking of peptidoglycan
D-cycloserin

Vancomycin
Bacitracin

Cephalosporin
Penicillin
Imipenem
Aztreonam
 Cell wall synthesis DNA replication
Cycloserine Quinolones
Bacitracin Nitroimidazoles
Beta lactams
Glycopeptides DNA

Folic acid Asam Folat

mRNA Rifampicin
metabolism
Asam Folat
50 50 50
Trimetoprim 30 30 30
Sulfonamid
Ribosomes

Cell membrane Protein synthesis

Polymixins Aminoglycosides
PABA
Macrolides
Lincosamides
Amphenicols (50S)
Tetracyclines (30S)
Structural characteristics of a bacterial cell
 Classification 1

Agents that either inhibits the synthesis of or disrupt bacterial

cell wall through enzyme activation

Examples: penicillins cephalosporins

Classification II

Agents that act on microbe cellular membrane, causing internal

compartment leaks

Examples: amphotericin B, polymixin

Classification III Classification IV
Agents that inhibit protein
Agents binding to the 30S ribosomal
synthesis, through ribosomal unit, inhibiting protein synthesis
disruption

Examples: chlorampenicol, Examples: the aminoglycosides such

erythromycin as garamycin and gentamycin
Classification V Classification VI

Agents that alter the synthesis Agents that inhibit specific metabolic
or metabolism of nucleic acids activity of the microbe

Examples: rifampin, nalidixic

Examples: sulfonamides
acid
Classification VII

Agents that bind to viral enzymes

preventing DNA synthesis, thus
preventing viral replication

Examples: acyclovar, vidarabine

 Bacteria are still survive
Drug tolerant after antibiotics treatment

>
Bacteria are able to destroy
Drug destroying antibacterial activities
Resis- (penisilinase)

tance
Genetic From chromosome

>
Related to bacteria which is
Non-genetic not multiplicating
 Bacterial resistance test

Example: ampicillin
Sensitive: Intermediate
Inhibition Zone ≥ 14 mm
Resistance: Susceptible
Inhibition Zone ≤ 11 mm
Resistant
 Site of infection

Bacterial Community/hospital
factors acquired

Details about the host (age, underlying

disease, predisposing factor)
 Bacteria by Site of Infection
Mouth Skin/Soft Tissue Bone and Joint
Peptococcus S. aureus S. aureus
Peptostreptococcus S. pyogenes S. epidermidis
Actinomyces S. epidermidis Streptococci
Pasteurella N. gonorrhoeae
Gramnegative rods
Abdomen Urinary Tract Upper Respiratory
E. coli, Proteus E. coli, Proteus S. pneumoniae
Klebsiella Klebsiella H. influenzae
Enterococcus Enterococcus M. catarrhalis
Bacteroides sp. Staph saprophyticus S. pyogenes

Lower Respiratory Lower Respiratory Meningitis

Community Hospital S. pneumoniae
S. pneumoniae K. pneumoniae N. meningitidis
H. influenzae P. aeruginosa H. influenza
K. pneumoniae Enterobacter sp. Group B Strep
Legionella pneumophila Serratia sp. E. coli
Mycoplasma, Chlamydia S. aureus Listeria
Infection Bacterials Antibiotics of choice

Meningitis N. meningitidis Benzilpenisi

H. influenzae Chloramphenicol
Acute follicular tonsilitis S. pyogenes Benzilpenisilin
Amoxycillin
Acute Otitis media S. pyogenes Amoxycillin
Sinusitis S. pyogenes Amoxcycillin
S. pneumoniae Amoxycillin
H. influenzae Amoxcycillin
Pneumonia S. pneumoniae Benzilpenisilin
M. pneumoniae Erythromycin
Endokarditis S. viridans Benzilpenisilin +
S. faecalis gentamicin
Pyelonefritis E. coli Amoxycillin
Urinary tract Infection E. coli Amoxycillin
Wound dan abscess S. aureus Flucloxacillin
Osteomyelitis S. aureus Flucloxacillin
Septic Arthritis S. aureus Flucloxacillin
Infection Bacterials Antibiotics of
choice
Trachoma Chlamydiae Tetracyclin
Non specific Urethritis Chlamydiae Tetracylin
Septicaemia E.coli
Acute Pyelonephritis Klebsiella Gentamicin
Pyelonephritis E. coli Co-trimoxazole
Urinary tract infection E. coli Co-trimoxazole
Biliary tract infection Enterobacter Gentamicin
Proteus Gentamicin
Ps. Aeruginosa Gentamicin +
ticarcillin
Intraabdominal infections Bacteroides spp Metronidazole
e.g. liver abscess
pelvic inflamm dis
cholangitis
peritonitis
Typhoid fever Salmonella typhi Chloramphenicol
 The bacterial, host, and drug factors that must be considered
when selecting antibiotic therapy
Bug factors Host factors Drug factors
• Identity of • Site of infection
pathogen(s) • Allergies
• Susceptibility of • Renal function
pathogen • Hepatic function
• Neutropenia
• Digestive tract function
• Other underlying diseases
• Concomitant medication
• Pregnancy
• Desired route of
administration
• Activity against
pathogen(s)
• Ability to get to site of
infection
• Potential for drug
interaction
• Dosing frequency (for
outpatient)
• Taste (for liquid
formulation)
• Stability at different
temperature (liquid
formulation)
• Cost
 Antibiotic Spectrum of Activity

No antibiotic is effective against all microbes

 Penicillins
O
S CH3
R C NH CH CH C
CH3
O C N CH COOH

B-lactam ring

Common nucleus
1. PENICILLIN
Wide therapeutic margin

Less effective for Gram (-)

Mostly destroyed by beta lactamase

Widely distributed in the body (esp. pleura,

peritoneal, sinovial fluid)

High concentration in urine

CSF < 1% (normal) & 5% (inflammed)

Underlying enterohepatic cycle (high concentration

in gall bladder)
 PENICILLIN

Activity Example

Active against Gram (+), Penisilin-G

destroyed by betalactamase

Stable in gastric Penisilin V, ampicilin,

juices amoxyciilin, cloxacilin

Active against Gram (+),

resistance to staphylococ Meticilin, nafsilin
producing betalactamase

Active against Gram (+) & (-), Ticarsilin, carbenisilin

destroyed by betalactamase
 PENICILLIN

Activity Example
Narrow spectrum, sensitive to Penisilin-G, benzatin penisilin,
beta-lactamase prokain penisilin, penisilin V

Narrow spectrum, resistance to Meticilin, oxacylin, nafsilin,

beta-lactamase kloksasilin, dikloksasilin

Broad spectrum aminopenisilin Ampicilin, amoxycillin

Extended spectrum, Ticarsilin, carbenisilin,

antipseudomonas piperasilin
 PENICILLIN

ADVERSE
EVENT
immediate: skin rash, anaphylactic,
wheezing
HipersensitivitY
Delayed: erythema, serum
sickness syndrome

interstitial nephritis, haemolytic anemia , netropenia,

pansitopenia, eosinofilia, drug fever, vaskulitis
PENICILLIN-G

Unstable in acid environment

After I.m, peak concent 15-30 mnt, and
decline
(t 1/2): 30 mnt

Serum & tissue concentration

• Up to 12 hrs (300.000 unit)
• Up to several days (2,4 juta unit)

10% are eliminated via glomerular filtration, 90%

via tubular secretion
Benzatin penicillin (1 mol penisilin + 2 mol
amonium base): in plasma up to 15-30 days
 Narrow spectrum, sensitive to beta-lactamase
Penicilin-G, benzatin penicilin, procain penicilin, penicilin V

Effective for: coccen Gram (+), Neisseria, and

Gram (-) anaerob,

Destroyed by beta-lactamase.

Infection by pneumococcus, streptococcus,

meningococcus, and gonococcus: penicillin G
0,6 – 5 million Unit (0,36-3 gr) i.m.
Narrow spectrum, sensitive to beta-lactamase
Penicilin-G, benzatin penicilin, procain penicilin, penicilin V

penicilin G: every 4 – 6 hours, infusion, severe

infection.

For mild infection (pharyngitis, sinusitis, and otitis

media): penisilin V per oral, 1 gr/hari, 4 times/day (5
days).

Pharyngitis due to Strept beta-hemolyiticus group A:

prophylaxis for RHD or glumorulonephritis
• penicillin V, 4 x 500 mg 10 days, or
• benzathine penisilin G, i.m 1,2 million unit,
(duration several weeks).
 Extended spectrum, antipseudomonas
Ticarcilin, carbenisilin, piperacilin

Carbenisilin and ticarcilin:

DOC for Pseudomonas aeruginosa

Sepsis due to pseudomonas:

Combined with
carbenisilin 12-30 gr/day ticarsilin 200-300 mg/kg
Gentamicin 5-7 mg/kg
iv or BB/day
BB/day i.m
Penicillins and Cephalosporins
O
S CH3
R C NH CH C H C
CH3
O C N CH COOH

Penicillin nucleus
B-lactam ring

O
S
R C NH CH C CH2 O

O C N C CH2 O C
C
CH3

Cephalosporin nucleus
2. CEPHALOSPORIN

Mostly parenteral.

Widely distributed in the body, only a

few penetrate CSF

High concent in urine: for UTI.

Concent in Gall bladder is much higher

than plasma
2. CEPHALOSPORIN

Cefoperazon and Ceftriaxon are excreted

via gall bladder

1st Generation esp active against Gram (+)

3rd Generation esp active against Gram (-

), weaker effect towards staphylococcus,