Antimicrobials drugs

Dr. Mohammed Al-Khawlani

Assist. Professor of pharmacology and Toxicology

1 Dr. M. Al-Khawlani
 Introduction of antimicrobials

❑ The term chemotherapy: was chemical substances (drugs) used to kill or stop growth of
infective microbes (Antimicrobials), now drugs to kill cancer cells (anti-cancer chemotherapy).

❖ Chemotherapy includes:

1. Antimicrobial Agents
➢ They include antibacterial, antifungal and antiviral drugs.

➢ Antibiotics: agents derived from living organisms (bacteria, fungi or mold) to be used
to kill or stop growth other microorganisms as Penicillins , cephalosporins ,
tetracyclines, chloramphenicol

➢ They are more selective on microorganisms with less toxic effects in human (Selective
toxicity), depend on the biochemical different between microbe and the host cell.

2. Antiparasitic Agents
➢ Anthelmintics and antiprotozoal drugs.

3. Anticancer Chemotherapy

2 Dr. M. Al-Khawlani
 Classification of Bacteria

❖ Bacterial structure

3 Dr. M. Al-Khawlani
 Classification of Bacteria

❖ Classification of Bacteria:
1. According to Pathogenicity
A- Non-pathogenic: as normal flora (Staphylococcus epidermidis, Lactobacillus acidophilus
B- Pathogenic: as Neisseria gonorrhea, Streptococcus pneumoniae.

2. According to Growth Requirement :

A- Aerobics: most of bacteria.
B- Anaerobic: as, clostridium spp.

3. According to Gram Staining :

A- Gram positive (Gm +ve)
B- Gram negative (Gm-ve)
C- Non-Gram Stain bacteria (Atypical bacteria): as Mycoplasma, Chlamydia , Mycobacteria
and Legionella.

4. According to shape of bacteria

- Cocci:

- Bacilli (Rods)
4 Dr. M. Al-Khawlani
 Classification of Bacteria
Types of pathogenic bacteria
Gram +ve bacteria

Gram +ve cocci Disease Gram+ve bacilli Disease

Staphylococci -Skin infections -Corynobacerium -Diphteria
-Acute endocarditis
*MSSA Surgical wounds
- MRSA -Osteomylitis
*Vancomycin resistant -Diabetic foot
-Urinary tract infections
Streptococci -Upper respiratory tract infections Bacillus anthrax Anthrax
• tonsillitis, pharyngitis, otitis,
sinusitis.

- Lower respiratory tract

infections: bronchitis &
pneumonia
-Sub acute endocarditis
(Rheumatic fever).
Enterococci -Peritonitis. Closterium -food poisoning
-Urinary tract infections botulonimi
-Gastroenteritis Clonstridium tetani -Tetanus
- Endocarditis
Listeria -Meningitis in
5 Dr. M. Al-Khawlani
monocytogenes neonates
 Classification of Bacteria
Gram –ve bacteria
Gram-ve cocci Disease Gram-ve bacilli Disease
-Neisseria meningitis Meningitis In respiratory tract
-Lower respiratory tract infect.
Niseeria gonorrhea Gonorrhea Hemophilus influenza - Meningitis

Potadella pertussus -Upper respiratory tract infect.

-Moraxella -Upper respiratory tract -In urinary tract infections

infections (URTI) (enterobacilli)
• tonsillitis, -E. coli, kelpsiella , proteus, -Urinary tract infections
pharyngitis, otitis, enterobactrer -Gastroenteritis
Serratia -Aspiration pneumonia
-Conjunctivitis -Neonatal meningitis
Pseudomonas
Pneumococi In small intestine
*Non penicillin producing -Meningitis Vibro cholera -Cholera
*Penicillin producing -Pneumoni -Salmonella typi&paratypi -Typhoid fever
-Brucella -Brucellosis
-yersenia -Plague
In large intestine
-shegella & salmonella Gastrointeritis
In stomach& duodenum
Helicobacter pylori -Peptic ulcer
Cambellobacter pylori -Deodenitis
Psudomonas -Urinary tract infections
-Nosocomial infections
-Infections in immuno-
6 Dr. M. Al-Khawlani
suppressed persons
 Classification of Bacteria

Anaerobes Disease Atypical bacteria Diseases

-Peptidococci -Localized abscess in In genital tract
lung ,brain , root of teeth -Treponema -Syphilis
-Peptidostreptococci , pelvis , genital organs
-Chlamydia - Uro-genital infect.
Pneumonia, Eye infections
(trachoma).

In central nervous
-Clostridium perfingis Gas gangrene system
Rickettsia -Rocky mountain fever

-Borrelia -Lyme diseases

-Clostridum difficle Pseudomembranous In respiratory tract

colitis Nocardia -Nocardiosis
Mycoplasma -Atypical pneumonia
Myobactrium TB -Tuberculosis
-Propriobacterium acne Acne valgais Bones Actinomycosis

G-ve = GIT, UTI, RTI, meningitis G +ve= RTI & skin

7 Dr. M. Al-Khawlani
 Classification of Bacteria

8 Dr. M. Al-Khawlani
 Antibacterial drugs

❖ Antibacterial drugs (Antibiotic)

▪ Drugs or chemical substances that used to inhibit the growth or kill bacteria
❖ Classification of antibacterial drugs:
1. According to their source:
A. Natural: from fungi e.g. Penicillin
from bacteria e.g. Gentamycin
B. Semisynthetic: e.g. Ampicillin
.

C. Synthetic: e.g. fluoroquinolones .

2. According to the activity of the drug:

a) Bacteriostatic: stop growth and multiplication of bacteria ( need active immune) e.g.
macrolides & tetracycline.

b) Bactericidal: kill the bacteria (no need active immune) e.g. B-lactam, vancomycin, and
aminoglycosides.
• used in serious infections as endocarditis, septicemia, and meningitis.

9 Dr. M. Al-Khawlani
 Anti- bacterial drugs

N.B.:
- few antibacterial may be bacteriostatic or bactericidal according to their concentration
or the state of activity of bacteria, e.g. erythromycin and isoniazid.

3. According to the spectrum of activity:

Broad spectrum Narrow spectrum

-Effective against multiple gram +ve &
Gm -ve organisms
Imipenem , tetracycline, quinolones
,chloramphenicol , cotrimoxazole
Used as initial empirical treatment till
culture ,sensitivity results appear
Rapid development of resistance
-Superinfection with resistant strains
and, pseudomembranous colitis are
common
10
-Effective against specific organisms
Antimicrobial against gram +ve bacteria
Erythromycin, clindamycin, vancomycin,
bacitracin, daptomycin, streptogramins &
linezolid, Penicillin G
Antimicrobial against gram -ve bacteria:
aminoglycosides ,aztreonam
-Used in treatment of susceptible organisms based
on culture and sensitivity results
Slow development of resistance
-Superinfection with resistant strains and
pseudomembranous colitis are less common
Dr. M. Al-Khawlani
 Antibacterial drugs

3. According to their mechanism of action:

a) Inhibitors of cell wall synthesis: As: B- Lactam, vancomycin, cycloserine.
b) Inhibitors of protein synthesis by:
-Inhibition of 30 S ribosomal subunit As: tetracycline, aminoglycosides
-lnhibition of 50 S ribosomal subunit: As macrolides & Chloramphenicol.
c) Inhibitors of nucleic acid synthesis: As: rifampicin, quinolones.
d) Inhibitors of cell membrane function: As: isoniazid.
e) Inhibitors of folic acid synthesis: As: sulphonamides.

11 Dr. M. Al-Khawlani
 Anti- bacterial drugs

❖ Antimicrobial Therapy

▪ Empirical therapy: use of antimicrobial agents before identification of causative

organism or availability of susceptibility test results.

- Immediate empiric therapy is indicated in critically ill or serious infections patient until
the result of culture and sensitivity test is revealed.
- Broad-spectrum therapy may be needed initially: e.g. Community-aquired pneumonia
with Macrolid or Fluoroquinolones

▪ Definitive therapy: use of antimicrobial agent after identification / susceptibility tests of

causative organism responsible for the disease.
- Narrow-spectrum therapy may be needed

- The antimicrobial agent should be selected according to the type of organism, culture and
sensitivity reports.

12 Dr. M. Al-Khawlani
 Antibacterial drugs

❖ Factors affecting Selection of antibacterial agent

❑ Identification of the infecting organism:

❑ Patient factors:
▪ In neonates, the use → toxic effect:
- chloramphenicol → gray baby syndrome .
- Sulfonamides → kernicterus (brain damage)

▪ In growing children, the use of:

- Fluoroquinolones → arthropathy
- Tetracyclines → abnormal teeth and bone formation.

▪ In old age (> 65 years): renal toxicity with

aminoglycosides is greater than in younger patients.

▪ In immunocompromised patients, the use of

bactericidal agents is necessary.

▪ Pregnancy: antibiotics cross the placenta and cause

adverse effects to the fetus e.g. aminoglycosides and
13 Dr. M. Al-Khawlani
tetracyclines. FDA categories of antimicrobials and fetal risk
 Antibacterial drugs

❑ The site of the infection: Lipid solubility, Molecular weight.

▪ Lipid soluble antibiotics e.g. prostate, and blood–brain barrier
- chloramphenicol and metronidazole can cross the barriers in normal conditions.
- Penicillin: cannot cross the barriers unless inflammation is present.

❑ The safety of the agent: penicillin are among the least toxic, chloramphenicol potential for
serious toxicity

❑ The cost of therapy & route of administration:

- Several drugs may show similar efficacy in treating an infection but vary widely in cost.

14 Dr. M. Al-Khawlani
 Antibacterial drugs

❖ Frequency Of Antibiotic Dosing

➢ Concentration-dependent killing:
- Bactericidal effect depends on drug concentration (↑ rate of bacterial killing as the
concentration of antibiotic increases)
- Aminoglycosides, Quinolones and daptomycin
- Giving by a single large dose per day → achieves high peak levels and cause rapid killing
of bacteria.

➢ Time-dependent killing:
- Bactericidal effect depends on the percentage of time that the drug concentration in the
blood remains above the MIC.
- β-lactam antibiotics, macrolides, clindamycin, and linezolid
- So, preparations with long duration kill more bacteria.

➢ Post-antibiotic effect (PAE):

- a persistent bacterial suppression after levels of antibiotic fall below the MIC.
- Antimicrobials with long PAE (e.g. aminoglycosides and fluoroquinolones, Erythromycin,
Tetracycline, Clindamycin, Streptogramins, linezolid) often require only one dose per day

15 Dr. M. Al-Khawlani
 Antibacterial drugs

❖ Combination Therapy

❖ Advantages of drug combinations:

- To achieve synergism. as β-lactams + aminoglycosides
- To reduce the incidence of bacterial resistance. As TB
- To broaden the spectrum. As Amoxicillin + Clavulanic acid.
- To treat mixed infections. Diabetic foot
- To treat serious infections as septicemia.

❖ Disadvantages of drug combinations:

• Bactericidal + bacteriostatic drugs → Antagonism ((cidal drugs act on active growing and
multiplying bacteria, e.g. tetracycline → ↓ penicillin efficacy)
• Development of antibiotic resistance by giving unnecessary combination therapy.
• ↑ risk of superinfection.

1. Static + Static → Addition.

2. Cidal + Cidal → Synergism.
3. Static + Cidal → Antagonism

16 Dr. M. Al-Khawlani
 Antibacterial drugs

❖ Antibacterial resistance

▪ Antibacterial resistance is the ability of bacteria to grow in the presence of a drug that
would normally kill them or limit their growth.

❑ Mechanism of resistance:
1- Synthesis of inactivating enzymes → destroy antimicrobial agents such as:
- Penicillinase produced by staphylococci, some streptococci , pneumococci , H. influenzas
- Acetyltransferase produced by Gram –ve bacilli → inactivate aminoglycosides and
chloramphenicol by transference of the acetyl group.

2- Inhibition of entry of antibiotics inside the bacterial cells eg

- pseudomonas and other Gm -ve bacilli inhibit the entry of aminoglycosides by loss or
mutation of porins

▪ efflux pump that can transport drugs out of the cell. such as tetracycline

3- Target modification:
▪ Modification of the target site by chromosomal change. As erythromycin and
fluoroquinolones)
▪ Alteration of bacterial penicillin-binding proteins. (Streptococci pneumoniae resistance to
17 Dr. M. Al-Khawlani
β-lactam)
 Antibacterial drugs

18 Dr. M. Al-Khawlani
 Antibacterial drugs

❖ Complication of antibacterial therapy:

1. Hypersensitivity (Anaphylactic reaction): Ex. Penicillins
▪ characterized by hypotension, bronchospasm, vascular collapse and may lead to shock..
▪ Treated mainly by adrenalin, hydrocortisone, antihistamines and oxygen.
▪ Test for allergy must be done. (Sensitivity test)

2. Direct toxicity
▪ High serum levels of certain antibiotics as; aminoglycosides may cause ototoxicity

3. Superinfections
▪ Broad-spectrum antimicrobials (as Clindamycin, fluoroquinolone) or combinations of
agents → kill of the normal flora → overgrowth of opportunistic organisms, especially
fungi or resistant bacteria as clostridium difficile → pseudomembranous colitis
(antibiotic-associated diarrhea).

• treatment by: 1- Stop used the antibacterial drugs

2- Metronidazole or Vancomycin orally
3- Antifungal as; nystatin for candidiasis

19 Dr. M. Al-Khawlani