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Case 1
Tunyapon Sasithorn
Pharmacology
Clinical case
Problem 1
 A clinical study evaluating the efficiency
of the antibiotic treatment of the
meningitis was carried out. One group
of patients with pneumococcal
meningitis received parenteral
penicillin. A second group received
penicillin plus tetracycline therapy.
A.
How do penicillin and
tetracycline differ in
their mechanism of
action?
Penicillin
Mechanism of Action
 B- lactam antibiotics work by inhibiting the
formation of peptidoglycan cross links in the
bacterial cell wall.
 The B- lactam moiety of penicillin binds to the
enzyme (transpeptidase) that links the
peptidoglycan molecules in bacteria, and this
weakens the cell wall of the bacterium when it
multiplies
 This causes cell cytolysis or death when the
bacterium tries to divide.
 The build-up of peptidoglycan precursors
triggers the activation of bacterial cell wall
hydrolases which further digest the bacteria's
existing peptidoglycan.
Tetracycline
Mechanism of Action
 Tetracyclines inhibit bacterial protein
synthesis by blocking the attachment of
the transfer RNA-amino acid to the
ribosome.
 They are inhibitors of the codonanticodon interaction.
Mechanism of Action
 Penicillin
 Bactericidal
 Tetracycline
 Bacteriostatic
2.
Which group had a
lower mortality rate?
Mortality was significantly higher in the
penicillin– tetracycline group compared
to the single drug penicillin group:
Mortality rate
Penicillin – tetracycline group

79%
∞one of seven patients survived
Penicillin group

30%
∞ nine of 20 patients survived
3.
If there was a
difference, what would
account for the
observation?
 Penicillin group experienced a bactericidal
effect which is very important in treating
patients with pneumococcal meningitis.
 Penicillin – tetracycline – a combination of a
cell wall agent, the bactericidal activity of which
depends on cell growth (penicillin), with a
reversible protein synthesis inhibitor that
interferes with cell growth (tetracycline), is a
classical example of antibiotic antagonism,
resulting in the lower mortality rate of
penicillin – tetracycline group.
 Antagonist reaction of Penicillin
and tetracycline renders these
drugs in combination ineffective.
 The mutual antagonist reaction
produces an overall bacteriostatic
activity which proves ineffective in
treating patients with
pneumococcal meningitis.
4.
Any other drug
combination that you
can recommend? On
what basis?
Other drug recommendations
due to:
 Meningitis with penicillin
resistant pneumococcus
 Other synergistic reaction
Drug combinations
 Drugs of first choice
Children
 Ceftriaxone
 Cefotaxime +/Vancomycin
Adults
 Ceftriaxone
 Cefotaxime
Others
 Rifampin
 B lactam antibiotic
 Ex: Penicillin, Ampicillin,
Piperacillin and Cefuroxime
+ Gentamicin
 Alternative drugs
Children
 Chloramphenicol
 Systematic
corticosteroids
Adults
 Vancomycin +
Ceftriaxone
 Vancomycin +
Cefotaxime
Thank You
sir, mam.
Come again!
:P