Antibiotic, anti-infective

antimicrobials drugs
ANTIMICROBIAL DRUGS CLASS

MODE OF ACTIONS
 Definition of Terms

• Antibiotics: Antibiotics are chemical substances produced from

various microorganisms (bacteria and fungi) that kill or inhibit the
growth of other microorganisms
• Antimicrobial drugs: Drugs that are used to treat infections with
micro- organisms are known as antimicrobial drugs.
• Chemotherapy: It means using chemical agents that are selectively
toxic to the causative agent of the disease, such as a microorganism
or malignant cells.
• Bacteriostatic: when a chemical substance inhibit bacterial growth
and proliferation
• Bactericidal: when a chemical substance kill bacteria
• Antibiotic resistance: is the ability of bacteria/fungi to resist the
effects of an antibiotic.
• Narrow spectrum: drugs which are effective against limited
number of microbes: Example: Polymyxin, Isoniazid, and
Vancomycin Broad-spectrum: Drugs which kill wide range of
microorganisms.
• Sepsis is a potentially life-threatening complication of an infection. Sepsis occurs
when chemicals released into the bloodstream to fight the infection trigger
inflammatory responses throughout the body damage multiple organ systems.
• Bacteremia : Bacteremia or Septicemia is the presence of viable bacteria in the
circulating blood.
• Super infection: a new infection occurring in a patient having a preexisting
infection; for example, bacterial infection may occur in patients with viral
respiratory disease.
• Infection, the invasion and multiplication of pathogenic microorganisms in body
tissues, causing disease by local cellular injury, secretion of a toxin or by antigen–
antibody reaction in the host.
 Common Microbes Causing Diseases
• Bacteria: anti bacterial
• Viruses: anti viral
• Fungi: anti fungal
• Protozoa: antiprotozoal
 Classification of Antibacterial Drugs
• Inhibitors of bacterial cell wall synthesis
• Inhibitors of bacterial protein synthesis
• Inhibitors of bacterial DNA synthesis
 Cell Wall Synthesis Inhibitors
• Penicillin are antibiotics derived from several strains of common
moulds.
• All penicillin's and cephalosporins have beta lactam ring, therefore
they are called Beta Lactam Antibiotics
 Peptidoglycan
• is polymer of sugars and amino acids. The sugar part is composed
of alternating units of N-acetylmuramic acid (NAMA) and N-
acetylglucosamine (NAGA).These alternating sugars are connected
by a glycosidic bond. A peptide chain (amino acids) is attached to
the NAMA which is crossed linked to amino acids chain on a
neighboring NAMA unit.
 Action of Penicillin and cephalosporin
• The synthesis of cell wall of bacteria is completely depended upon an enzyme
named as transpeptidase (Penicillin binding proteins (PBPs)).
• This enzyme cross- links peptidoglycan chains to form rigid cell walls.
• Penicillin and cephalosporin's inhibits the cell wall of bacteria by irreversibly
blocking transpeptidase action.
• A critical part of the process is the recognition of the D-Ala-D-Ala sequence of
the NAMA peptide side chain by the PBP. Interfering with this recognition
disrupts the cell wall synthesis.
• β-lactams mimic the structure of the D-Ala-D-Ala link and bind to the active site
of PBPs, disrupting the cross-linking process.
 Therapeutic Uses
• Bacterial infections (only Peptidoglycan cell walled bacteria)
• Side effects and contraindications (self study)

• Antimicrobial resistance: is the ability of microbes to resist the effects of

drugs in same dosage.
• When the drug loose the ability to either kill or inhibit the growth of
microbes and the microbes gain the ability to survive in the presence of
drug to which they were previously susceptible this is called resistance.
• Intrinsic resistance: is the innate ability of a bacterial species to resist activity of
a particular antimicrobial. This can also be called insensitivity since it occurs in
organisms that have never been susceptible to that particular drug.
• Lack of affinity of the drug for the bacterial target for example penicillin's are not
effective against mycobacterium tuberculosis, as the later does not contain
peptidoglycan in cell wall. mycoplasma which does not have cell wall is
naturally resistant to beta lactams.
• Inaccessibility of the drug into the bacterial cell For example: gram negative
bacteria are naturally resistant to vancomycin and penicillin because of inability
to penetrate outer membrane. Also, anaerobic bacteria are naturally resistant to
aminoglycosides, because there is lack of oxidative metabolism to drive uptake
of aminoglycosides.
• Acquired resistance: means when the microbes gains the ability to grow
in the presence of a drug. Acquired resistance develops when micro-
organisms (bacteria, fungus, parasites or viruses) no longer respond to a
drug to which they were previously susceptible.

• Cephalosporin drugs are beta lactam antibiotics that inhibit the cell wall
of bacteria. Cephalosporin C was first isolated from a fungus named as
Cephalosporium acremonium by Dr. Abraham in 1948.
• These are bactericidal antibiotics as they kill the micro-organisms when
used at therapeutic dose.
Mode of Action: of Cephalosporin, As penicillin
• First Generation: The optimum activity of all first generation
cephalosporin drugs is against gram- positive bacteria such as
staphylococci and streptococci. Drugs Examples:
• Cefazolin
• Cefadroxil
• Cephradine
• Cephalexin
• Second Generation:
• The second generation drugs have more activity against gram- negative bacteria
(Hemophilus influenzae, Enterobacter aerogenes) in comparison to the first
generation. Their gram positive spectrum is less than the first generation.
• Drugs:
• Cefamandole
• Cefoxitin
• Cefaclor
• Cefpodoxime
Third Generation:
Third generation cephalosporin drugs are broad spectrum and the effective against
both gram positive and gram negative bacteria.
Drugs:
Cefotaxime
Ceftriaxone
Ceftazidime
Cefixime
• Fourth Generation: These are extended spectrum antibiotics. They are resistant
to beta lactamases.
• Drugs:
• Cefepime
• Fifth Generation Cefazoline, and Ceftobiprole are broad spectrum, advanced-
generation cephalosporins that is administered IV. They are the only
commercially available β-lactam in the United States with activity against MRSA
and is indicated for the treatment of complicated skin and skin structure
infections and community-acquired pneumonia. The unique structure allows
cefazoline to bind to PBP2a found with MRSA and PBP2x found with
Streptococcus pneumoniae.