1-Intro. Antibiotic Oct 14th 2018-Modified

Introduction to the antimicrobial agents
Fadhel Ahmed Alomar, Ph.D.

Dept. of Pharmacology, College of Clinical Pharmacy, IAU
falomar@iau.edu.sa
 Antimicrobial drugs are used to eradicate microorganisms or inhibit
their growth
 Microorganisms include bacteria, viruses, fungi, and parasites
 The vast majority of microorganisms are not harmful to humans but

are beneficial (nonpathogenic organisms )
 Normal bacterial flora of the small intestine produce vitamin K &
prevent colonization of the intestine with pathogenic bacteria
 E. coli can be manipulated to produce desired protein e.g insulin
 Less than 1% of bacteria, can invade our body and cause disease
 Classes of antimicrobial agents
1. Disinfectants
 Substances used to kill a wide range of microorganisms on the no-
living surface to prevent the spread of illness
2. Antiseptics
 Substances used to kill a wide range of microorganisms on the
living tissue to prevent infection during injury or surgery
3. Antibiotics
 Substances produced by one microbe that has the ability to inhibit
or kill another microorganism
Introduction to the antimicrobial drugs
 Antimicrobial agents are ligands whose receptors are microbial
proteins
 Antimicrobial agents are classified according to the microorganisms
they act primarily against
1. Antibiotics, also known as antibacterials, are used against bacteria
 Anti-tuberculous medications are used to treat Tuberculosis (TB)
2. Antifungal medications are used to treat and prevent mycosis
3. Antiviral medications are used specifically for treating viral infections
4. Antiparasitic medications are used for the treatment of parasitic diseases
 Parasites include protozoa and helminths (worms)

General principles of antibiotic drugs
I. Bactericidal drugs
 Direct kill bacteria & their activities dependent on the bacterial cell
proliferation (growth) & concentration of antibiotics
 Some dying bacteria release toxins that cause
tissue/organ damage
II. Bacteriostatic drugs

 Indirect kill bacteria
 Inhibit the growth of bacteria without killing the microorganisms, THUS
 Normal host immune system is required to remove the microorganisms
from the body
 Caution with immunocompromised patient (HIV & cancer)

 Bactericidal agents is highly recommenced rather than
bacteriostatic agents to treat compromised patients
III. Post antibiotic effects (PAEs) phenomenon
 Definition:
 The length of time that bacterial growth is suppressed after a brief
exposure of organisms to an antibiotic agent (in vitro & in vivo)
 Factors that affect the duration of PAE
1. Type of antibiotic
 Compared to cell wall synthesis inhibitor antibiotic, protein
synthesis inhibitor (aminoglycosides) & nucleic acid synthesis
(fluoroquinolones) inhibitor antibiotics induce longer-term PAE
 Antimicrobial combinations enhances the duration of the PAE
2. Duration of antibiotic exposure
3. Bacterial species
4. The concentration of antibiotic
 Concentration-Dependent Bactericidal Action and the PAE
MIC = minimum inhibitory concentration; lowest concentration that inhibits growth

MBC = minimum bactericidal concentration; lowest concentration that reduces number
General principles of antimicrobial chemotherapy
 The mechanisms of PAEs include
III. Slow recovery of bacterial after non-lethal dose of antibiotic
IV. Persistence of antibiotics at binding site within microorganisms
V. Alteration in the DNA functions
VI. Requirement to synthesize new proteins before growth restarts
 Clinical importance of the PAEs:

1. Determination of the PAE provide an important information for
evaluation of new antibiotics (preclinical phase)
2. In general, antibiotics with no PAEs require more frequent
administration than those that demonstrate PAEs
o Aminoglycosides (AG) & fluoroquinolones have PAEs against
Gram –ve bacteria up to four hours
o The most beta-lactam (except for imipenem) have no PAEs
against G –ve
IV. Using the combination of antibiotics
 In general, single antibiotic drug is should be used (less cost &
less side effects)
 Indications (situations require using a combination of antibiotics)
1. To achieve synergistic effects (Amoxicillin & Gentamicine)
2. To prevent the emergence of antibiotic resistant (TB)
3. To be used as initial therapy to treat severe infections of unknown
etiology (e.g. systemic infection; sepsis)
4. To treat mixed bacterial infections (polymicrobial bacterial infection)

IV. Using the combination of antibiotics
 Disadvantages
1. Drug antagonism may occur (penicillin plus tetracycline)
o Bacteriostatic can antagonize bactericidal drugs
 Try to combine drugs that bactericidal together or
bacteriostatic together
2. Increases the risk of adverse effects
3. Increases the risk of drug resistant superinfection

V. Selection of antibiotics
 Microbial identification (Gram +ve or Gram -ve) & susceptibility testing
by using MIC give valuable information to select the best antibiotic,
dose & the serum concentration of the antibiotic to treat infection
VI. Empiric therapy

 The administration of antibiotics without knowledge of the cause of
infection based on experience
1. When the organism is most likely known (less expensive)
2. When delay in starting treatment would threaten the life of the
patient; (Meningitis; a dangerous infection & associated with high
risk of death)
VII. Prophylactic therapy
1. Given before potential exposure or after known exposure to
pathogenic organisms (meningitis)
2. Surgery –given within 1 hour of procedure and not more than 24

hours afterwards
3. Prevent opportunistic infections

 Anticancer agents increase risk of infection )
4. Recurrent infections, and those exposed to individuals with

sexually transmitted diseases (STDs)
Problems associated with antibiotics
administration
Problems associated with antibiotics
administration
I. Superinfection
II. Antibiotic Resistance

I-Superinfection
 A new infection taking place during treatment of a primary infection
 Example: clostridium difficile-associated diarrhea (CDAD)
o CDAD results from disruption of the normal bacterial flora

o This disruption usually is caused by broad-spectrum antibiotics such
as clindamycin
o It can lead to severe complications such as watery or bloody diarrhea
watery, pseudomembranous colitis & sepsis
 Metronidazole is DOC for treatment of CDAD
“Antibiotics are the only class of drugs whose
efficacy begins to diminish immediately after
they are released for clinical use.”
II-Antibiotic Resistance
 It is a major concern associated with overuse of antibiotics
 It is occurred when an organism that would normally be sensitive to
an antibiotic becomes resistant to it
 Bacteria develop resistant to antibiotics through genetic mutation or
by accepting antibiotic resistant gene from other bacteria (circular
DNA called plasmid)

II-Antibiotic Resistance
 Drug resistance is divided into two major types:
I. Primary resistance refers to cases originally infected with
resistant organisms e.g. methicillin resistant staphylococcus
aureus (MRSA) in the hospital
II. Acquired resistance refers to resistant that develops during
treatment
Risk factors for antibiotic Resistance
1. History of treatment with antibiotic drugs (overuse of antibiotics)
2. Inappropriate treatment regimens ( received inadequate dose and/
or duration)
3. Contacts of persons with antibiotic-resistant (TB patients with
multiple drug resistance)
4. Immunocompromised patients
5. The rate of antimicrobial resistance is significantly increased in the
hospital particularly in the intensive care units (ICUs) because of..
a. Broad spectrum and/or inappropriate antimicrobial usage
b. Prolonged length of stay in hospital
Mechanism of antibiotic resistance
1. Inactivation of antibiotic drug
 Production of drug-metabolizing enzymes (beta lactamase) that open
the beta-lactam ring (penicillin & cephalosporine)
2. Chang in the target sites for the antibiotic (mutation)

 Change in peincillin-binding protein; transpeptidase (MRSA)
 Alteration of 50S ribosomal subunit by methylation of adenine (target
for clarithromycin)
 Mutation in the DNA gyrase (target for ciprofloxacin )
Mechanism of antibiotic resistance
3. Alteration of metabolic pathway
 Bacteria use para-amino benzoic acid (PABA) as a precursor for folic
acid synthesis (folic acid is essential for DNA & RNA synthesis)
 Sulfonamide drugs (sulfamethoxazole) interfere with folic acid synthesis
o Sulfonamide-resistant bacteria increase PABA production
4. Reduced antibiotic accumulation inside microorganism

 Decreasing drug permeability (aminoglycoside)
 Increasing active efflux (pumping out) of the drugs across the cell
surface (tetracycline)
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Introduction to the antimicrobial agents

Fadhel Ahmed Alomar, Ph.D.

 The vast majority of microorganisms are not harmful to humans but

 E. coli can be manipulated to produce desired protein e.g insulin

1. Antibiotics, also known as antibacterials, are used against bacteria

 Anti-tuberculous medications are used to treat Tuberculosis (TB)

2. Antifungal medications are used to treat and prevent mycosis

3. Antiviral medications are used specifically for treating viral infections

4. Antiparasitic medications are used for the treatment of parasitic diseases

 Parasites include protozoa and helminths (worms)

II. Bacteriostatic drugs

 Caution with immunocompromised patient (HIV & cancer)

MIC = minimum inhibitory concentration; lowest concentration that inhibits growth

 Clinical importance of the PAEs:

 Indications (situations require using a combination of antibiotics)

1. To achieve synergistic effects (Amoxicillin & Gentamicine)

2. To prevent the emergence of antibiotic resistant (TB)

3. To be used as initial therapy to treat severe infections of unknown

etiology (e.g. systemic infection; sepsis)

4. To treat mixed bacterial infections (polymicrobial bacterial infection)

1. Drug antagonism may occur (penicillin plus tetracycline)

o Bacteriostatic can antagonize bactericidal drugs

 Try to combine drugs that bactericidal together or

2. Increases the risk of adverse effects

3. Increases the risk of drug resistant superinfection

VI. Empiric therapy

2. Surgery –given within 1 hour of procedure and not more than 24

3. Prevent opportunistic infections

4. Recurrent infections, and those exposed to individuals with

II. Antibiotic Resistance

o CDAD results from disruption of the normal bacterial flora

 It is occurred when an organism that would normally be sensitive to

an antibiotic becomes resistant to it

 Bacteria develop resistant to antibiotics through genetic mutation or

by accepting antibiotic resistant gene from other bacteria (circular

DNA called plasmid)

I. Primary resistance refers to cases originally infected with

resistant organisms e.g. methicillin resistant staphylococcus

aureus (MRSA) in the hospital

II. Acquired resistance refers to resistant that develops during

2. Chang in the target sites for the antibiotic (mutation)

4. Reduced antibiotic accumulation inside microorganism

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