This document defines various terms related to chemotherapy and antimicrobial drugs. It discusses how antibiotics like penicillin work by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs). It notes that penicillin was the first effective antibiotic discovered in 1928 by Alexander Fleming. Resistance can be intrinsic, due to properties of the bacterial species, or acquired through genetic changes. Later generations of cephalosporin antibiotics were developed with broader spectra of activity against both gram-positive and gram-negative bacteria through resistance to beta-lactamases. Fifth generation cephalosporins like ceftaroline maintain activity against methicillin-resistant Staphylococcus aureus.

1. Dr. Haji Bahadar,
Assistant Professor KMU-IPMS
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2. Definitions:
 Chemotherapy: It means using chemical agents that are selectively toxic to
the causative agent of the disease, such as a microorganism or malignant
cells.
 Antimicrobial drugs: Drugs that are used to treat infections with micro-
organisms are known as antimicrobial drugs.
 Antibiotics: Antibiotics are chemical substances produced from various
microorganisms (bacteria and fungi) that kill or inhibit the growth of other
microorganisms.
 Bacteriostatic: when a chemical substance inhibit bacterial growth and
proliferation
 Bactericidal: when a chemical substance kill bacteria
 Antibiotic resistance: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.
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3.  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 Septicaemia 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.
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Chlamydia trachomatis.

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6. Common microbes causing diseases
 Bacteria......anti bacterial
 Viruses……anti viral
 Fungi………anti fungal
 Protozoa ……antiprotozoal
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9.  Before penicillin introduction there was no effective treatment for
infections. In 1928 penicillin, the first true antibiotic, was discovered
by Alexander Fleming, Professor of Bacteriology at St. Mary's Hospital
in London. Alexander Fleming was a bit disorderly in his work. He left
his petridishes uncovered. Upon returning from holidays he noticed that
a fungus, Penicillium notatum, had contaminated a culture plate
of Staphylococcus bacteria. The fungus had created bacteria-free zones
wherever it grew on the plate. Fleming isolated and grew the mould in
pure culture. He found that P. notatum proved extremely effective even
at very low concentrations, preventing Staphylococcus growth even
when diluted 800 times. Fleming published his findings in the British
Journal of Experimental Pathology in June 1929.
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1. Inhibitors of bacterial cell wall synthesis
2. Inhibitors of bacterial protein synthesis
3. Inhibitors of bacterial DNA synthesis

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14.  Penicillins are antibiotics derived from several strains of common moulds.
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All penicillin's and cephalosporins have beta lactam ring,
therefore they are called beta lactam antibiotics

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16.  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.

16Diaminopimelic acid (DAP)

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18. 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. Penicillins 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.
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19.  Bacterial infections (only Peptidoglycan cell walled
bacteria)
 Side effects and contraindications (self study)
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20.  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.
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21.  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 –ve bacteria are naturally resistant to
vancomycin and penicillin G/V. 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.
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22.  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.
 Each year in the United States, at least 2 million people
become infected with bacteria that are resistant to
antibiotics and at least 23,000 people die each year as a
direct result of these infections.
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Penicillin-binding protein
2a (Staphylococcus aureus)

25.  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: As penicillin
 First Generation: The optimum activity of all first
generation cephalosporin drugs is against gram-
positive bacteria such as
staphylococci and streptococci.
Drugs:
 Cefazolin
 Cefadroxil
 Cephradine
 Cephalexin
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26.  Second Generation:
 The second generation drugs have more activity against gram-
negative bacteria (Haemophilus 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:
 Cefipime
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27. Fifth Generation
 Ceftaroline, and Ceftobiprole are broadspectrum, 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
ceftaroline to bind to PBP2a found with MRSA and PBP2x
found with Streptococcus pneumoniae.
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