BY
Prof. DR. Zainalabideen A. Abdulla,
DTM&H., MRCPI, Ph.D., FRCPath. (U.K.)

Any drug used to treat any condition or disease
Chemotherapeutic agents used to treat infectious diseases:
- Anti-Bacterial
- Anti-Viral
- Anti-Fungal
- Anti-Protozoal

- A substance produced by a microorganism that is effective in killing or inhibiting the growth of other organisms
- Anti-Bacterial
Examples :
- Mould-produced: Erythromycin, Chloramphenicol
- Bacteria-produced: Penicillin, Cephalosporin
(mainly soil bacteria)

1. Natural AB e.g. Peniciilin G
2. Semisynthetic AB, e.g. Modified AB (Ampicillin, Carbenicillin)
3. Synthetic Antimicrobials e.g. Monobactam (Aztreonam)

Bacteriostatic : Inhibit growth of bacteria
- Should NOT be used in immunocompromised or leukopenic patients
Bactericidal : Kill bacteria
Selective toxicity : Affect microorganisms NOT human cells

Cont./ … Antibacterial Agents
Narrow-spectrum antibiotic : Destroy (affect) either gram positive or gram negative bacteria
- Examples: Vancomycin: G+
Colistin : G-
Broad spectrum antibiotic : Destroy (affect) both gram positive and gram negative bacteria
- Examples: Ampicillin
Chloramphenicol
Tetracycline

Competitive inhibitors
- Example Sulfonamide
- See the Figure
- Inhibition of Nucleic Acid synthesis
Inhibition of cell wall synthesis
- Interfere with synthesis and cross-linking of peptidoglycan
- Human cells NOT affected;
WHY
?

- Beta-lactam drugs
- Actively dividing bacteria
- Bactericidal
Natural penicillin :
• Penicillin-G, Penicillin-V
• Against: G+ such as Strep., some anaerobes,
Spirochetes
G-: N. meningitidis , H. influenzae
-Aminopenicillin & Extended: G- infection

1. First generation: G+
2. Second generation: Increased activity G-
3. Third generation: Greater G- & Pseudomonas
4. Fourth generation: G+ & G- ; P. aeruginosa
5. Fifth generation (e.g. Ceftaroline) G+ including methicillin-resistant Staph. and G-

- Beta-lactam drug
- Active against gram negative rods
Not against gram positive bacteria
Not against anaerobes
Example : Aztreonam

- Beta lactam drug
- Active against most G+, G-, and anaerobes
Examples
• Imipenem : Inactivated by dihydropeptidase
(renal tubules); protected by Cilastatin
• Meropenem : Not inactivated by DHP enzyme
• Ertapenem: Not P. aeruginosa , long acting

- Broad-spectrum
- Action on ribosome (inhibit protein synthesis)
- Bacteriostatic
Effective against :
• G+ and G- bacteria
• Chlamydia
• Mycoplasma
• Rickettsias
• Vibrio cholera
• Spirochete ( Borrelia , Treponema pallidum )

- Broad-spectrum (against many G-, some G+,
NOT anaerobes, WHY?
):
• Enterobacteriaceae
• V. cholera
• P. aeruginosa
- Bactericidal
- Inhibit protein synthesis
- Ototoxic, Nephrotoxic

- Inhibit protein synthesis
• Bacteriostatic (low doses)
• Bactericidal (Higher doses)
Effective against :
. Many G+, some G- bacteria
. Chlamydia
. Mycoplasma
. T. pallidum
. Legionella

- Bactericidal
- Inhibit DNA synthesis
- Example: Ciprofloxacin ; effective against:
. Enterobacteriaceae
. P. aeruginosa

- To kill all bacteria, and to prevent resistance
- Example:
Mycobacterium tuberculosis :
(isoniazid + rifampin + pyrazinamide + ethambutol)

Degree of killing that is far greater than that achieved by either drug alone or the sum of both
Example : Co-trimoxazole (Trimethoprim + sulfamethoxazole)
Degree of killing that is less than that achieved by either drug alone
Example : Penicillin + Tetracycline (
)

- Toxic to patients ( WHY?
)
Mechanism of action :
1. Binding cell membrane sterol e.g. Nystatin, Amphotericin-B
2. Interfere with sterol synthesis e.g. Clotrimazole, miconazole
3. Blocking mitosis, or nucleic acid synthesis e.g. Griseofulvin, 5-flucytosine

- Toxic to human cells ( WHY?
)
Mechanism of action
1. Interfere with DNA and RNA synthesis e.g. Chloroquine, pentamidine, quinacrine
2. Interfere with protozoal metabolism e.g. Metronidazole (Flagyl)

- Few agents available
WHY?
- see your textbook
- Examples:
• Anti-HIV: Zidovudine (azidothymidine “AZT”);
1989

- Drug resistant bacteria (Superbugs)
- Superbugs USUALLY Multidrug Resistant
- Viruses/HIV, Fungi, Protozoa, Helminthes
(Also, Multidrug Resistant)
- See the Table

• MRSA, MRSE
• VISA, VRSA;
• VRE (UTI)
• P. aeruginosa
• Clostridium difficile
• Acinetobacter baumanni
• Klebsiella pneumonia
• M. tuberculosis (MDR-TB)

- Lack specific target, e.g. M. pneumoniae
- Intrinsic resistance: Natural
- Acquired resistance: Changed/Acquired
- FOUR mechanisms (See the Table)
- Resistance Factor ( R- Factor ); Conjugation
- MDR Pumps (Transporter/ Efflux Pump)

- Beta-lactam antibiotics with Beta-lactam ring
- Two types:
1. Penicillinases
2. Cephalosporinases
- Some bacteria produce one or both enzymes

Combine antibiotics with Inhibitors:
Examples :
Clavulanic acid + Amoxicillin = Augmentin
Clavulanic Acid + Ticarcillin = Timentin
Sulbactam + Ampicillin = Unasyn
Tazobactam + Piperacillin = Zosyn

- Education, Prudent use
- Proper prescription ( most unnecessary )
- First: Narrow spectrum & inexpensive
- Complete the full coarse as prescribed
- No need for prophylactic unless by clinician
- Good infection control and prevention

To “ guess”; “educated guess” :
• Pocket chart/Antibiogram (Clinical Microbiology Lab)
• Allergy
• Age
• Pregnancy
• Inpatients
• Site of infection, e.g. Brain, bladder?
• Drug cross-reaction
• Toxic side effects
• Immune status
• Cost

Undesirable effects of antimicrobial agents
• Selecting for drug-resistant organisms
• Allergy
• Toxic, e.g. Chloramphenicol Aplastic Anemia
Streptomycin Deafness
• Superinfection “ population explosion ”
By opportunistic or secondary invaders
Example: C. difficile antibiotic-associated/ pseudomembranous colitis
Candida albicans Yeast vaginitis